Plus, these new robots can heal themselves after being cut, giving them a longer life span. "They're neither a traditional robot nor a known species of animal. It's a new class of artifact: a living, programmable organism," notes Joshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research.

The live robots were designed and developed on a supercomputer at UVM and then tested by biologists at Tufts University. The idea of manipulating living organisms and copying body forms for human benefit isn't something new. However, this is the first time scientists have developed biological machines from scratch.

The team led by lead author and doctoral student Sam Kriegman, used an evolutionary algorithm to develop thousands of candidate designs for the new life-forms on the Deep Green supercomputer and was published in PANS. The program was fed the basic rules about biophysics of what a single frog skin and cardiac cells were capable of.

Nearly a hundred independent algorithm runs were conducted to select the most promising designs. Next, the team at Tufts worked with microsurgeon to transfer the silicon designs into life. Stem cells from an African frog (Xenopus lavevis, giving the name Xenobots) were harvested in the embryos. Assembled into body forms, the cells began working together.

Many of our gadgets and other technologies are made of steel, plastic, silicon. While it makes it strong and flexible, it also creates an ecological imbalance and human health problems. Bongard notes that living tissues are weak and degrade quickly. "But organisms have 4.5 billion years of practice at regenerating themselves and going on for decades," he says.

Even when tissues die, they're harmless to the environment. What's more interesting is that the live robots were sliced into half and surprisingly, it stitched itself and kept going. "This is something you can't do with typical machines," Bongard says. This is organic computation, which the authors explain as the information is shared and cooperated between cells.

The reconfigured organisms were found moving coherently and could explore watery environments for days and weeks together. The immediate application the researchers are suggesting is healthcare, where the Xenobots can be sent to pick a payload like medicine and carry it to the specific place inside the patient.

What About Ill-Effects?

Of course, the concerns on rapid changes in technology and complex biological manipulations have been rising. "When we start to mess around with complex systems that we don't understand, we're going to get unintended consequences," the scientists agree. At the same time, researchers note that a better understanding of complex properties is essential for mankind to survive.

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Scientists Develop Live Robots With Frog Cells That Might Redefine Healthcare - Gizbot

Cardiac Stem Cells Comments Off on Scientists Develop Live Robots With Frog Cells That Might Redefine Healthcare – Gizbot | January 17th, 2020

Forget gleaming metal droids -- the robots of the future may have more in common with the average amphibian than with R2D2.

A team of scientists have found a way to not just program a living organism, but to build brand new life-forms from scratch using cells, creating what researchers are calling xenobots.

Tiny in size, but vast in potential, these millimetre-sized bots could potentially be programmed to help in medical procedures, ocean cleanup and investigating dangerous compounds, among other things.

"They're neither a traditional robot nor a known species of animal, said researcher Joshua Bongard in a news release. It's a new class of artifact: a living, programmable organism."

In the introduction for the research published in Proceedings of the National Academy of Sciences (PNAS) on Monday, researchers point out that the traditional building blocks weve used for robots and tech -- steel, plastic, chemicals, etc. -- all degrade over time and can produce harmful ecological and health side-effects.

After realizing that the best self-renewing and biocompatible materials would be living systems themselves, researchers decided to create a method that designs completely biological machines from the ground up.

The bots are made out of stem cells taken from frog embryos -- specifically, an African clawed frog called xenopus laevis, which supplied the inspiration for the name xenobot. To design the xenobots, the possible configurations of different cells were first modeled on a supercomputer at the University of Vermont.

The designs then went to Tufts University, where the embryonic cells were collected and separated to develop into more specialized cells. Then, like sculptors (if sculptors used microsurgery forceps and electrodes), biologists manually shaped the cells into clumps that matched the computer designs.

Different structures were sketched out by the computer in accordance with the scientists goal for each xenobot.

For example, one xenobot was designed to be able to move purposely in a specific direction. To achieve this, researchers put cardiac cells on the bottom of the xenobot. These cells naturally contract and expand on their own, meaning that they could serve as the xenobots engine, or legs, and help move the rest of the organism, which was built out of more static skin cells.

In order to test if the living robots were truly moving the way they were designed to, and not just randomly, researchers performed a test that has stumped many a living creature.

They flipped the robot on its back. And just like a capsized turtle, it could no longer move.

When researchers created further designs for the bots, they found that they could design them to push microscopic objects, and even carry objects through a pouch.

"It's a step toward using computer-designed organisms for intelligent drug delivery," says Bongard.

The possible uses for these tiny robots are numerous, researchers say.

In biomedical settings, one could envision such biobots (made from the patients own cells) removing plaque from artery walls, identifying cancer, or settling down to differentiate or control events in locations of disease, the research paper suggests.

A robot made out of metal or steel generally has to be repaired by human hands if it sustains damage. One major benefit that researchers found of creating these robots out of living cells was how they reacted to physical damage.

A video taken by the researchers showed that when one of their organisms was cut almost in half by metal tweezers, the two sides of the wound simply stitched itself back together.

These living robots, researchers realized, could repair themselves automatically, something you cant do with typical machines, Bongard said.

Because they are living cells, they are also naturally biodegradable, Bongard pointed out. Once theyve fulfilled their purpose, theyre just dead skin cells, making them even more optimal for usage in medical or environmental research.

Although scientists have been increasingly manipulating genetics and biology, this is the first time that a programmable organism has been created from scratch, researchers say.

This new research takes scientists a step closer to answering just how different cells work together to execute all of the complex processes that occur every day in animals and humans.

"The big question in biology is to understand the algorithms that determine form and function," said co-leader Michael Levin in the press release. He directs the Center for Regenerative and Developmental Biology at Tufts.

"What actually determines the anatomy towards which cells co-operate? he asked. You look at the cells we've been building our xenobots with, and, genomically, they're frogs. It's 100 per cent frog DNA -- but these are not frogs. Then you ask, well, what else are these cells capable of building? As we've shown, these frog cells can be coaxed to make interesting living forms that are completely different from what their default anatomy would be.

Of course, a biological organism created and programmed by humans which is capable of healing itself might sound a little alarming. After all, one of the sponsors of the research is the Defense Advanced Research Projects Agency, which is affiliated with the U.S. military.

Researchers acknowledged in the press release that the implications around such technological and biological advancements can be worrying at times.

That fear is not unreasonable, Levin said. However, he believes that in order to move forward with science, we should not hold back from complex questions. This study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences.

"I think it's an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex," Levin says. "A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?"

More on this story from CTVNews.ca

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The 'xenobot' is the worlds newest robot and it's made from living animal cells - The Loop

Cardiac Stem Cells Comments Off on The ‘xenobot’ is the worlds newest robot and it’s made from living animal cells – The Loop | January 17th, 2020

Under normal circumstances the stem cells of frog embryos would skin and heart tissue of living beings, however, the progress of scientific knowledge has turned them into the first ever living robots.

Scientists from the University of Vermont with the help of special algorithms modified stem cells of a frog and created of them the first xenobot clumps of cells, capable of self-organization and even to transport tiny cargo. These colonies of 500-1000 cells do not resemble any living organism, or a naturally functioning body. At the same time they are different from the traditional robot is alive, but programmed organisms.

The opportunity to design a live guided machine, able to perform various tasks, from drug delivery to environmental cleanup, is truly revolutionary.

To create xenobot required a supercomputer and an algorithm that assemble in the desired configuration, hundreds of heart cells and skin tissue and simulates the result of such a living designer. The least successful configuration of the scientists involved in the experiment, culled, best preserved and improved using manipulations of the cells of the African frog Xenopus laevis microscopic tweezers and the electrode.

In one of the configurations, the scientists there is a hole in the center of the clot to reduce the resistance when driving. The experiment revealed that it can be used to attach to the get of goods for transportation.

After completing the Assembly of the fabric of biorobots began to operate at the programmed scenario: the skin cells began to group together, and provided the cardiac motor function. In an aqueous medium in the Petri dish these living machines can move up to a week without nutrient requirements energy supply inherent nature in the form of lipids and proteins.

Scientists say that this experiment gives an invaluable experience of knowing how cells communicate and exchange information:

From the point of view of the genome, its a frog. 100% DNA xenobot corresponds to the frog, but not frog. The question arises what else can be built from these cells? says biologist Michael Levin. This experiment shows us that frog cells can form life-forms that have nothing to do with the fact that they were anatomically.

However, living these robots can be called only conditionally they are not able to develop, you do not have the reproductive function and cant reproduce without the will of man, and, having exhausted all the resources of nutrients, they turn into lumps of dead cells (100% Biodegradability is a clear advantage of biological robots before the metal or plastic robots).

So far, the level of development xenobot seems completely harmless, but in the future they can enrich and nerve cells or even to turn into a new form of biological weapons.

Under normal circumstances the stem cells of frog embryos would skin and heart tissue of living beings, however, the progress of scientific knowledge has turned them into the first ever living robots.

Scientists from the University of Vermont with the help of special algorithms modified stem cells of a frog and created of them the first xenobot clumps of cells, capable of self-organization and even to transport tiny cargo. These colonies of 500-1000 cells do not resemble any living organism, or a naturally functioning body. At the same time they are different from the traditional robot is alive, but programmed organisms.

The opportunity to design a live guided machine, able to perform various tasks, from drug delivery to environmental cleanup, is truly revolutionary.

To create xenobot required a supercomputer and an algorithm that assemble in the desired configuration, hundreds of heart cells and skin tissue and simulates the result of such a living designer. The least successful configuration of the scientists involved in the experiment, culled, best preserved and improved using manipulations of the cells of the African frog Xenopus laevis microscopic tweezers and the electrode.

In one of the configurations, the scientists there is a hole in the center of the clot to reduce the resistance when driving. The experiment revealed that it can be used to attach to the get of goods for transportation.

After completing the Assembly of the fabric of biorobots began to operate at the programmed scenario: the skin cells began to group together, and provided the cardiac motor function. In an aqueous medium in the Petri dish these living machines can move up to a week without nutrient requirements energy supply inherent nature in the form of lipids and proteins.

Scientists say that this experiment gives an invaluable experience of knowing how cells communicate and exchange information:

From the point of view of the genome, its a frog. 100% DNA xenobot corresponds to the frog, but not frog. The question arises what else can be built from these cells? says biologist Michael Levin. This experiment shows us that frog cells can form life-forms that have nothing to do with the fact that they were anatomically.

However, living these robots can be called only conditionally they are not able to develop, you do not have the reproductive function and cant reproduce without the will of man, and, having exhausted all the resources of nutrients, they turn into lumps of dead cells (100% Biodegradability is a clear advantage of biological robots before the metal or plastic robots).

So far, the level of development xenobot seems completely harmless, but in the future they can enrich and nerve cells or even to turn into a new form of biological weapons.

See original here:
The first robots (xenobot) from living cells use cells of a frog - http://www.MICEtimes.asia

Cardiac Stem Cells Comments Off on The first robots (xenobot) from living cells use cells of a frog – www.MICEtimes.asia | January 17th, 2020

Otology sponges are cotton balls used after otology surgery. They are placed in the ear to hold the skin and eardrum in place after otology surgery. After otology surgery, the ear canal is packed with antibiotic ointment and otology sponges. Myringotomy with the insertion of tympanostomy tubes is the most common ontology surgical procedure in the U.S., and approximately 2 million procedures conducted each year. The field of otology has witnessed remarkable advancements in the management of complex ailments, such as hearing disorders, through the ongoing progress of sophisticated intricate and microscopic surgeries.

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Most common causes of surgeries are the retraction of the tympanic membrane, chronic otitis media and collapsed eustachian tube. Otology sponges are sterile devices used post-surgery for 6 weeks or for a month. Otology surgeries are mostly performed in outpatient systems and they do not require overnight stay. Since patients can go outdoor immediately after surgery, the chances of wound infection increase.

To prevent infection, these sponges are placed in ear canal with the lubrication of antibiotics. Sometimes, an incision is made behind the year to operate the internal canal. In this situation, sterile dressings along with antibiotic lubricants are placed over the stiches to prevent microbial infection. Owing to the shape of the ear, there is very less pace to operate inside it, owing to which otology surgeries are performed with the help of microscopes for greater accuracy and success. Increase in the number of ENT specialists, coupled with the availability of technologically sound surgical methods, is boosting the number of otology surgeries.

Otology Sponges Market: Drivers and Restraints

An increase in the number of otology surgeries due to the availability of advanced surgical methods is expected to drive the market. Advanced methods of otology surgeries have spread significantly in the developing world, which is also contributing to the growth of the market. Ease of use due to flexibility and the compressed configuration of these sponges is also driving the market.

Otology sponges are sterile and available in different sizes, hence, they are effective in preventing ear canal infections. Increase in awareness about the availability of otology surgical treatment is contributing to market growth. The effectiveness of otology sponges in preventing ear canal infections and holding the shape of the eardrum is driving the market. However, low awareness among the general public about their usage is restraining market growth.

Otology Sponges Market: Segmentation

The global otology sponges market can be segmented on the basis of material, end user type and geography.

Based on material type, the otology sponges market is segmented as:

Based on end use, the otology sponges market is segmented as:

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Otology Sponges Market: Overview

The global otology sponges market is expected to grow steadily owing to an increase in the number of otology surgeries. Advanced technological intervention for otology surgeries is also boosting the otology sponges market. By material type, the otology sponges market is expected to be dominated by latex-free otology sponges. By end users, the otology sponges market is expected to be dominated by ENT clinics owing to an increase in the number of outpatient surgeries. The widespread availability of otology sponges in different sizes makes them easy to use and one can wear them comfortably. Moreover, the number of otology surgical procedures has increased in developing countries as well, which is boosting the market in these countries.

Otology Sponges Market: Regional Outlook

The global otology sponges market is majorly dominated by North America owing to a significant number of otology surgical procedures in the region. Europe is the second most lucrative market owing to the availability of advanced otology surgical methods. Asia Pacific is expected to emerge as one of the most lucrative otology sponges markets owing to an increase in awareness about otology surgical treatments. Emerging economies, such as China and India, are potential markets for otology sponges because of their large population base. Latin America is also a lucrative market owing to the higher adoption of otology sponges. However, the Middle East and Africa is the least lucrative otology sponges market due to lack of awareness and the low availability of advanced otology surgical methods.

Otology Sponges Market: Key Players

Some of the global key players operating in otology sponges market areDeRoyal Industries, Inc.; Boston Medical Products, Inc.; Summit Medical, Inc.; American Surgical Company LLC; Medtronic and Olympus Corporation.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

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Cell Therapy And Tissue Engineering Market Size 2020 by Top Leading Companies- BioCardia Betalin Therapeutics, MEDIPOST Co., MaxCyte BioReliance...

IPS Cell Therapy Comments Off on Cell Therapy And Tissue Engineering Market Size 2020 by Top Leading Companies- BioCardia Betalin Therapeutics, MEDIPOST Co., MaxCyte BioReliance… | January 16th, 2020

SAN DIEGO--(BUSINESS WIRE)-- Allele Biotechnology and Pharmaceuticals, Inc. (President and CEO: Jiwu Wang, Ph.D., Allele), a San Diego-based private company, and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., Astellas), through its Massachusetts-based subsidiary Astellas Institute for Regenerative Medicine (AIRM), entered into a licensing agreement to expand Astellas access to Alleles induced pluripotent stem cell (iPSC) technologies for various cell therapy programs.

Astellas, one of the largest pharmaceutical companies in Japan and already a leader in the development of cell-based therapeutics, has further dedicated to development of the field through its commitment to state-of-the-art iPS cell generation, modification, and manufacturing. iPSC lines can differentiate into all somatic tissue types, enabling a wide variety of therapeutic applications. The field of iPSC-derived cells has seen dramatic growth in clinical trials recently--the majority of the ~12 clinical trials around the world were initiated within the last 18 months and many more are upcoming.

Allele has been developing its core strength in reprogramming somatic cells into iPSCs with granted patents and the first commercial cGMP system it developed over the past 10 years. Allele also engages in more than a dozen different human tissue derivation activities through its own R&D efforts for internal programs and partnerships. To realize the unparalleled potential of iPSC, Alleles researchers and cGMP team are committed to setting up and validating cell assays for product quality control, genome analysis pipelines, closed-system automation for reprogramming, and machine learning in iPSC-related fields.

Under the terms of the new license agreement, Astellas will pay Allele upfront and milestones, product-based royalties, and potentially manufacture fees.

About Allele Allele Biotechnology and Pharmaceuticals was founded in 1999. In 2015, the company completed an 18,000 square foot state-of-the-art facility in San Diego for the production of GMP-grade human iPSC lines. The facility also supports the production of tissue-specific cells differentiated from these iPSCs, including pancreatic beta cells, neural progenitor cells, and cardiomyocytes.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200113005668/en/

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Allele and Astellas Enter into an Expanded License for the Development of iPSC Lines - BioSpace

IPS Cell Therapy Comments Off on Allele and Astellas Enter into an Expanded License for the Development of iPSC Lines – BioSpace | January 16th, 2020

Stafford Township, NJ Stem cell therapy is an incredible process for healing damaged tissue, so it seems remarkable that it is availablefor petsright here in Manahawkin. Stafford Veterinary Hospital, at 211 North Main St., began offering the advanced treatment in 2019, under the direction of Michael Pride, medical director at the facility.

There, stem cell therapy is most commonly applied to osteoarthritis, but can also be used in dogs suffering from hip dysplasia and ligament and cartilage injuries, as well as mobility ailments and some chronic inflammatory issues such as inflammatory bowel disease and chronic kidney disease, which is common in cats.

Stem cell therapy is actually the only thing that can help to reverse the process of arthritis, Pride said. Everything else is a Band-Aid.

This process can actually help to rebuild cartilage and really reduce inflammation without the need of using aspirin-type medications, Pride said. Its a newer technology that we can use to avoid chronic use of medications, which might actually be detrimental in the long term for the liver or kidneys.

Stem cell therapy treats the source of the problem by offering the ability to replace damaged cells with new ones, instructs the website staffordvet.com.

Stem cells are powerful healing cells in the pets body that can become other types of cells. For example, in the case of arthritis, stem cells can become new cartilage cells and have natural anti-inflammatory properties, thus reducing pain and increasing mobility.

The stem cells are your primary structural cell for all other cells in the body; they can differentiate into almost any other cell, explained Pride. Were processing it down into that primordial stem cell; were activating it, and were injecting it into where it needs to be, and it just starts taking on the characteristics of the cells around it.

Table-top machines from MediVet Biologics are the first Adipose Stem Cell therapy kits for in-clinic use, a major advancement. Stem cell therapy for animals has been commercially available since 2004. MediVet pioneered in-clinic treatment options around 2010.

Pride believes Stafford Veterinary Hospital offers the only such treatment in the immediate area; another is in Egg Harbor Township, Atlantic County.

Were always trying to figure out different ways to help the patient without hurting them, he said while petting a kitten that had been a patient for another type of treatment.

As stem cell therapy is more in the news regarding humans, a pet owners first question might be where the stem cells come from that are used in the process. The answer: from fat tissue of the pet itself, extracted and processed the same day.

As the therapy has been refined in the last decade, it has actually started to become a lot easier, more cost-effective more recently, said Pride, since weve been able to process fat tissue instead of actually getting bone marrow.

Fat tissue actually has a much higher concentration of adult stem cells than bone marrow does, so its less painful for the patient, they heal a lot easier, and we dont have to process it in a different facility.

Everything comes from the animal, and we give it back to the animal. Nothing comes from another animal. We dont have to worry about them rejecting the sample; its their own tissue, and were giving it back to them.

The pet typically goes home the same day after about eight hours. First, X-rays and a consultation with the veterinarian can determine whether the pet is a candidate for the treatment.

A pet owner may not even know that their animal has arthritis.

Cats have a lot of inflammatory issues that they tend to be very good at hiding, said Pride. A lot of people dont realize that they have arthritis. They think, oh, my cats just getting older; hes not jumping as much; hes not as strong; hes just sleeping most of the day, but actually he has arthritis. Its very difficult to diagnose in cats. A lot of times you end up having to do X-rays to find where the arthritic joints happen to be.

An inch-and-a-half incision is the minor surgery that harvests the fat tissue from the belly while the pet is anesthetized. For a cat, about 20 gramsare extracted. For a large dog, about 40 gramsare needed. While the pet is recovering from the incision surgery, the veterinary hospital is processing the sample. When the sample is ready, the pet is sedated because we then have to give them the joint injections. Then we can reverse the sedation, and they go home.

We asked the doctor if the process always works. He gave the example that on average, a dog such as a boxer that was hobbled is now able to walk without seeming like its painful. In an extreme positive case, a dog that had been barely walking might be bouncing all over the place in two months.

It doesnt always work to the extent that we would love it to, but we usually notice that there is a positive effect from it, Pride remarked. Every patient will be different in what they experience.

For the same reason that everyones situation is going to be different, cost of treatment was not given for this story.

It generally takes about 30 to 60 days for relief to show, the veterinarian said, and the animals progress will be monitored.

On average, results last about 18 months to two years before more stem cells might have to be injected. The procedure takes about an hour.

The nice thing is once we collect those stem cells (from the first procedure), we can bank the leftovers they are cryogenically stored at MediVet corporate headquarters in Kentucky and we dont have to go through the initial anesthetic surgery, said Pride.

Stem cell therapy is one of several innovative modalities available at Stafford Veterinary Hospital. Laser therapy, acupuncture and holistic medicine are others. Care for exotic pets is available, as is emergency pet care.

Visit the website staffordvet.com or call 609-597-7571 for more information on general and specialized services, including: vaccinations, microchipping, spayingand neutering, dental care, wellness exams, dermatology, gastrology, oncology, opthalmology, cardiology, soft-tissue surgery, ultrasound, radiography, nutrition, parasite control, boarding, laborand delivery, end-of-life care, and cremation.

Stafford Veterinary Hospital has been in business since 1965, founded by Dr. John Hauge. Today, five highly skilled veterinarians are on staff, and a satellite, Tuckerton Veterinary Clinic, is at 500 North Green St. in Tuckerton.

Pride has been medical director at Stafford Veterinary Hospital since 2008. He attended Rutgers University, then earned his Veterinary of Medicine degree at Oklahoma State University.

The mild-mannered doctor feels a great rewardfrom treating animals that cant speak for themselves when they feel bad.

These guys, theyre always thankful; you can see what they think, he said of treated pets. The turnaround in their attitude, the turnaround in their ability to be more comfortable, you can see it in their faces; you can see it in their actions. You learn to read animals over time.

Its knowing that were helping those who cant help themselves, he added, and you can see it in them; thats the most gratifying.

mariascandale@thesandpaper.net

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Stem Cell Therapy for Dogs and Cats Is Innovative at Stafford Veterinary Hospital - By MARIA SCANDALE - The SandPaper

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy for Dogs and Cats Is Innovative at Stafford Veterinary Hospital – By MARIA SCANDALE – The SandPaper | January 16th, 2020

LONDON, UK / ACCESSWIRE / January 15, 2020 / Hemogenyx Pharmaceuticals plc (HEMO.L) ("Hemogenyx" or the "Company"), the biopharmaceutical group developing new therapies and treatments of blood diseases, is pleased to announce the following update on its activities.

As previously announced, Hemogenyx's CDX product has the potential to treat Acute Myeloid Leukemia (AML) directly as well as providing a benign conditioning regimen for blood stem cell replacement therapy. The Company has now carried out extensive work developing treatments for AML and has to date obtained encouraging results.

Hemogenyx has successfully constructed and in vitro tested Chimeric Antigen Receptor (CAR) programmed T cells (HEMO-CAR-T) for potential treatment of AML. HEMO-CAR was constructed using Hemogenyx's proprietary humanized monoclonal antibody against a target on the surface of AML cells. The Company has demonstrated that HEMO-CAR was able to programme human T cells (converted them into HEMO-CAR-T) to identify and destroy human AML derived cells in vitro.

Following the successful completion of these tests, in vivo tests of the efficacy of HEMO-CAR-T against AML are being conducted utilising a model of AML using Advanced peripheral blood Hematopoietic Chimera (ApbHC) - humanized mice developed by Immugenyx, LLC, a wholly-owned subsidiary of Hemogenyx.

Vladislav Sandler, Chief Executive Officer, commented, "We are encouraged by this new data which demonstrates our continuing progress in the development of novel treatments for blood cancers such as AML. The development of HEMO-CAR-T expands Hemogenyx's pipeline and advances it into a cutting-edge area of cell-based immune therapy. We are excited to have developed another product candidate that should, if successful, provide a new and potentially effective treatment for blood cancers for which survival rates are currently very poor."

About AML and CAR-T

AML, the most common type of acute leukemia in adults, has poor survival rates (a five-year survival rate of less than 25% in adults) and is currently treated using chemotherapy, rather than the potentially more benign and effective form of therapy being developed by Hemogenyx. The successful development of the new therapy for AML would have a major impact on treatment and survival rates for the disease.

CAR-T therapy is a treatment in which a patient's own T cells, a type of immune cell, are modified to recognize and kill the patient's cancer cells. The procedure involves: isolating T cells from the patient, modifying the isolated T cells in a laboratory using a CAR gene construct (which allows the cells to recognize the patient's cancer); amplifying (growing to large numbers) the newly modified cells; and re-introducing the cells back into the patient.

Market Abuse Regulation (MAR) Disclosure

Certain information contained in this announcement would have been deemed inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 until the release of this announcement.

Enquiries:

Hemogenyx Pharmaceuticals plc

http://www.hemogenyx.com

Dr Vladislav Sandler, Chief Executive Officer & Co-Founder

headquarters@hemogenyx.com

Sir Marc Feldmann, Executive Chairman

SP Angel Corporate Finance LLP

Tel: +44 (0)20 3470 0470

Matthew Johnson, Vadim Alexandre, Soltan Tagiev

Peterhouse Corporate Finance Limited

Tel: +44 (0)20 7469 0930

Lucy Williams, Duncan Vasey

US Media enquiries

Tel: +1 (323) 646-3249

Lowell Goodman

lowell@corbomitecomms.com

About Hemogenyx Pharmaceuticals plc

Hemogenyx Pharmaceuticals plc ("Hemogenyx") is a publicly traded company (HEMO.L) headquartered in London, with its wholly-owned US operating subsidiaries, Hemogenyx LLC and Immugenyx LLC, located in New York City at its state-of-the-art research facility and a wholly-owned Belgian operating subsidiary, Hemogenyx-Cell SPRL, located in Lige.

Hemogenyx is a pre-clinical stage biopharmaceutical group developing new medicines and treatments to bring the curative power of bone marrow transplantation to a greater number of patients suffering from otherwise incurable life-threatening diseases. Hemogenyx is developing several distinct and complementary product candidates, as well as a platform technology that it uses as an engine for novel product development.

For more than 50 years, bone marrow transplantation has been used to save the lives of patients suffering from blood diseases. The risks of toxicity and death that are associated with bone marrow transplantation, however, have meant that the procedure is restricted to use only as a last resort. Hemogenyx's technology has the potential to enable many more patients suffering from devastating blood diseases such as leukemia and lymphoma, as well as severe autoimmune diseases such as multiple sclerosis, aplastic anemia and systemic lupus erythematosus (Lupus), to benefit from bone marrow transplantation.

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Hemogenyx's CAR-T Cells are Effective Against AML in vitro - Yahoo Finance

Bone Marrow Stem Cells Comments Off on Hemogenyx’s CAR-T Cells are Effective Against AML in vitro – Yahoo Finance | January 16th, 2020

Cancer enters your body when cells begin to grow out of control. There are various types of cancer and cells in almost every part of the body can become cancer. Leukemia is a type of cancer which starts in the cells, then develops into different types of blood cells. It starts in early forms of white blood cells. There are different types of leukemia which can be divided into acute and chronic. Acute is fast growing and chronic is slow growing.

An Acute Lymphoblastic Leukemia is a type of leukemia which progresses quickly and if not treated, will be fatal in a couple of months. Acute means fast growing and lymphatic means it develops from the early forms of lymphocytes, which is a type of white blood cell. It all starts in the bone marrow and leukemia cells start to invade the body quickly. They can spread to other parts of the body. Some cancers also start in the organs and then spread to the bone marrow, but they are not leukemia.

There are other types of cancer which start in lymphocytes and are known as lymphomas. Leukemias affect blood and bone marrow and lymphomas affect lymph nodes and other organs. It can sometimes be difficult to tell if a cancer of lymphocytes is lymphoma or leukemia. If at least 20% of the bone marrow has cancerous lymphocytes, the disease is considered to be leukemia. Acute Lymphoblastic Leukemia is the most common childhood cancer and children below the age of five are at the highest risk. It can also occur in adults.

RELATED:Kids Born To Obese Mothers Are More Likely To Develop Leukemia

ALL can increase the chances of bleeding and developing infections in the body. Its symptoms include:

In order to diagnose ALL, the doctor must complete a physical exam and also conduct bone marrow tests and blood tests. Doctors are likely to ask about bone pain, since it is the most common symptom of ALL. Here are a few tests doctors carry out.

The doctor might order a blood count, and people who have ALL may have a blood count which shows low platelet count and a low hemoglobin count. The WBC may or may not have increased. A blood smear might show immature cells circulating in the blood, which are usually found in bone marrow.

This process involves taking a sample of the bone marrow from your breastbone or the pelvis. It is an ideal way to test for increased growth in marrow tissue and reduced production of red blood cells.

An X-ray of the chest can allow the doctor to see if the mediastinum, that is the middle partition of the chest is widened. Further, a CT scan can help the doctor estimate whether the cancer has spread to the spinal cord, brain or to any other part of the body.

There are other tests like a spinal tap, which is used to check if cancer cells have spread around the spinal fluid. Tests on the serum urea and liver function might also be done.

The treatment will help bring the count back to normal. When this happens and the bone marrow looks normal, the cancer is in remission. Acute Lymphoblastic Leukemia can be treated through chemotherapy. You might be asked to stay at the hospital for a few weeks in the first treatment. Later, you can continue the treatment as an outpatient.

For those with a low WBC count, you will be asked to spend time in an isolation room. It ensures that you are protected from contagious diseases and other problems. If leukemia does not respond to chemotherapy, a bone marrow or stem cell transplant might be recommended. The transplanted marrow can be taken from a sibling who is a complete match.There are high chances of cancer remission in case of children.

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What happens when you take cells from frog embryos and grow them into new organisms that were "evolved" by algorithms? You get something that researchers are calling the world's first "living machine."

Though the original stem cells came from frogs the African clawed frog, Xenopus laevis these so-called xenobots don't resemble any known amphibians. The tiny blobs measure only 0.04 inches (1 millimeter) wide and are made of living tissue that biologists assembled into bodies designed by computer models, according to a new study.

These mobile organisms can move independently and collectively, can self-heal wounds and survive for weeks at a time, and could potentially be used to transport medicines inside a patient's body, scientists recently reported.

Related: The 6 Strangest Robots Ever Created

"They're neither a traditional robot nor a known species of animal," study co-author Joshua Bongard, a computer scientist and robotics expert at the University of Vermont, said in a statement. "It's a new class of artifact: a living, programmable organism."

Algorithms shaped the evolution of the xenobots. They grew from skin and heart stem cells into tissue clumps of several hundred cells that moved in pulses generated by heart muscle tissue, said lead study author Sam Kriegman, a doctoral candidate studying evolutionary robotics in the University of Vermont's Department of Computer Science, in Burlington.

"There's no external control from a remote control or bioelectricity. This is an autonomous agent it's almost like a wind-up toy," Kriegman told Live Science.

Biologists fed a computer constraints for the autonomous xenobots, such as the maximum muscle power of their tissues, and how they might move through a watery environment. Then, the algorithm produced generations of the tiny organisms. The best-performing bots would "reproduce" inside the algorithm. And just as evolution works in the natural world, the least successful forms would be deleted by the computer program.

"Eventually, it was able to give us designs that actually were transferable to real cells. That was a breakthrough," Kriegman said.

The study authors then brought these designs to life, piecing stem cells together to form self-powered 3D shapes designed by the evolution algorithm. Skin cells held the xenobots together, and the beating of heart tissue in specific parts of their "bodies" propelled the 'bots through water in a petri dish for days, and even weeks at a stretch, without needing additional nutrients, according to the study. The 'bots were even able to repair significant damage, said Kriegman.

"We cut the living robot almost in half, and its cells automatically zippered its body back up," he said.

"We can imagine many useful applications of these living robots that other machines can't do," said study co-author Michael Levin, director of theCenter for Regenerative and Developmental Biologyat Tufts University in Massachusetts. These might include targeting toxic spills or radioactive contamination, collecting marine microplastics or even excavating plaque from human arteries, Levin said in a statement.

Creations that blur the line between robots and living organisms are popular subjects in science fiction; think of the killer machines in the "Terminator" movies or the replicants from the world of "Blade Runner." The prospect of so-called living robots and using technology to create living organisms understandably raises concerns for some, said Levin.

"That fear is not unreasonable," Levin said. "When we start to mess around with complex systems that we don't understand, we're going to get unintended consequences."

Nevertheless, building on simple organic forms like the xenobots could also lead to beneficial discoveries, he added.

"If humanity is going to survive into the future, we need to better understand how complex properties, somehow, emerge from simple rules," Levin said.

The findings were published online Jan. 13 in the journal Proceedings of the National Academy of Sciences.

Originally published on Live Science.

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Scientists have created the worlds first living robots out of frog stem cells, according to new research. These tiny new lifeforms can be programmed to move around or carry and deliver miniature payloads that could one day be medicines inside a patients body, the Guardian reports.

The scientists knit skin and heart cells scraped from the embryos of African clawed frogs (Xenopus laevis) into 3D shapes designed by artificial intelligence to accomplish certain tasks.

These are entirely new lifeforms. They have never before existed on Earth, study co-author Michael Levin told the Guardian. They are living, programmable organisms.

The living robots, called xenobots after the clawed frogs Latin name, measure 0.04 inches and have enough energy inside them to keep moving for seven to 10 days before calling it quits.

The squishy robots dont have the strength and durability of plastic or metal machines, but biology affords them some unique advantages. They can heal themselves if wounded, and when their biological engines run out of fuel the xenobots simply fall apart and decay. This last part is crucial when it comes to potential medical or environmental applications in which leaving behind shards of plastic or metal presents obvious problems.

The researchers said we cant know for sure what applications await the soft-bodied bots, but imagined uses including cleaning up microplastics in the ocean, digesting toxic materials at polluted sites or scooping plaque from inside human arteries. Apart from scooting around in petri dishes, the researchers also say tinkering with these living machines could help scientists better understand the software of life.

The first generation of xenobots are tiny, but the scientists say the plan is to scale up perhaps even to living robots with blood vessels and nervous systems that can live on dry land.

If the voice of Jeff Goldblums character from Jurassic Park is beginning to echo in the back of your mind, youre not alone: When youre creating life, you dont have a good sense of what direction its going to take, Nita Farahany, who studies the ethics of new technologies and was not involved in the study, told Smithsonian. Any time we try to harness life [we should] recognize its potential to go really poorly.

For their part, the creators of the xenobots acknowledged the potential ethical implications, but say its up to society and policymakers to decide what those might be.

I think theyd acquire moral significance only if they included neural tissue that enabled some kind of mental life, such as the ability to experience pain, ethicist Thomas Douglas told the Guardian. But some are more liberal about moral status. They think that all living creatures have interests that should be given some moral consideration. For these people, difficult questions could arise about whether these xenobots should be classified as living creatures or machines.

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Research Results

SCIENCE

Newswise A book is made of wood. But it is not a tree. The dead cells have been repurposed to serve another need.

Now a team of scientists has repurposed living cells--scraped from frog embryos--and assembled them into entirely new life-forms. These millimeter-wide "xenobots" can move toward a target, perhaps pick up a payload (like a medicine that needs to be carried to a specific place inside a patient)--and heal themselves after being cut.

"These are novel living machines," saysJoshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research. "They're neither a traditional robot nor a known species of animal. It's a new class of artifact: a living, programmable organism."

The new creatures were designed on a supercomputer at UVM--and then assembled and tested by biologists at Tufts University. "We can imagine many useful applications of these living robots that other machines can't do," says co-leader Michael Levin who directs theCenter for Regenerative and Developmental Biologyat Tufts, "like searching out nasty compounds or radioactive contamination, gathering microplastic in the oceans, traveling in arteries to scrape out plaque."

The results of the new research were published January 13 in theProceedings of the National Academy of Sciences.

BESPOKE LIVING SYSTEMS

People have been manipulating organisms for human benefit since at least the dawn of agriculture, genetic editing is becoming widespread, and a few artificial organisms have been manually assembled in the past few years--copying the body forms of known animals.

But this research, for the first time ever, "designs completely biological machines from the ground up," the team writes in their new study.

With months of processing time on the Deep Green supercomputer cluster at UVM'sVermont Advanced Computing Core, the team--including lead author and doctoral student Sam Kriegman--used an evolutionary algorithm to create thousands of candidate designs for the new life-forms. Attempting to achieve a task assigned by the scientists--like locomotion in one direction--the computer would, over and over, reassemble a few hundred simulated cells into myriad forms and body shapes. As the programs ran--driven by basic rules about the biophysics of what single frog skin and cardiac cells can do--the more successful simulated organisms were kept and refined, while failed designs were tossed out. After a hundred independent runs of the algorithm, the most promising designs were selected for testing.

Then the team at Tufts, led by Levin and with key work by microsurgeon Douglas Blackiston--transferred the in silico designs into life. First they gathered stem cells, harvested from the embryos of African frogs, the speciesXenopus laevis. (Hence the name "xenobots.") These were separated into single cells and left to incubate. Then, using tiny forceps and an even tinier electrode, the cells were cut and joined under a microscope into a close approximation of the designs specified by the computer.

Assembled into body forms never seen in nature, the cells began to work together. The skin cells formed a more passive architecture, while the once-random contractions of heart muscle cells were put to work creating ordered forward motion as guided by the computer's design, and aided by spontaneous self-organizing patterns--allowing the robots to move on their own.

These reconfigurable organisms were shown to be able move in a coherent fashion--and explore their watery environment for days or weeks, powered by embryonic energy stores. Turned over, however, they failed, like beetles flipped on their backs.

Later tests showed that groups of xenobots would move around in circles, pushing pellets into a central location--spontaneously and collectively. Others were built with a hole through the center to reduce drag. In simulated versions of these, the scientists were able to repurpose this hole as a pouch to successfully carry an object. "It's a step toward using computer-designed organisms for intelligent drug delivery," says Bongard, a professor in UVM'sDepartment of Computer ScienceandComplex Systems Center.

LIVING TECHNOLOGIES

Many technologies are made of steel, concrete or plastic. That can make them strong or flexible. But they also can create ecological and human health problems, like the growing scourge of plastic pollution in the oceans and the toxicity of many synthetic materials and electronics. "The downside of living tissue is that it's weak and it degrades," say Bongard. "That's why we use steel. But organisms have 4.5 billion years of practice at regenerating themselves and going on for decades." And when they stop working--death--they usually fall apart harmlessly. "These xenobots are fully biodegradable," say Bongard, "when they're done with their job after seven days, they're just dead skin cells."

Your laptop is a powerful technology. But try cutting it in half. Doesn't work so well. In the new experiments, the scientists cut the xenobots and watched what happened. "We sliced the robot almost in half and it stitches itself back up and keeps going," says Bongard. "And this is something you can't do with typical machines."

CRACKING THE CODE

Both Levin and Bongard say the potential of what they've been learning about how cells communicate and connect extends deep into both computational science and our understanding of life. "The big question in biology is to understand the algorithms that determine form and function," says Levin. "The genome encodes proteins, but transformative applications await our discovery of how that hardware enables cells to cooperate toward making functional anatomies under very different conditions."

To make an organism develop and function, there is a lot of information sharing and cooperation--organic computation--going on in and between cells all the time, not just within neurons. These emergent and geometric properties are shaped by bioelectric, biochemical, and biomechanical processes, "that run on DNA-specified hardware," Levin says, "and these processes are reconfigurable, enabling novel living forms."

The scientists see the work presented in their newPNASstudy--"A scalable pipeline for designing reconfigurable organisms,"--as one step in applying insights about this bioelectric code to both biology and computer science. "What actually determines the anatomy towards which cells cooperate?" Levin asks. "You look at the cells we've been building our xenobots with, and, genomically, they're frogs. It's 100% frog DNA--but these are not frogs. Then you ask, well, what else are these cells capable of building?"

"As we've shown, these frog cells can be coaxed to make interesting living forms that are completely different from what their default anatomy would be," says Levin. He and the other scientists in the UVM and Tufts team--with support from DARPA's Lifelong Learning Machines program and the National Science Foundation-- believe that building the xenobots is a small step toward cracking what he calls the "morphogenetic code," providing a deeper view of the overall way organisms are organized--and how they compute and store information based on their histories and environment.

FUTURE SHOCKS

Many people worry about the implications of rapid technological change and complex biological manipulations. "That fear is not unreasonable," Levin says. "When we start to mess around with complex systems that we don't understand, we're going to get unintended consequences." A lot of complex systems, like an ant colony, begin with a simple unit--an ant--from which it would be impossible to predict the shape of their colony or how they can build bridges over water with their interlinked bodies.

"If humanity is going to survive into the future, we need to better understand how complex properties, somehow, emerge from simple rules," says Levin. Much of science is focused on "controlling the low-level rules. We also need to understand the high-level rules," he says. "If you wanted an anthill with two chimneys instead of one, how do you modify the ants? We'd have no idea."

"I think it's an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex," Levin says. "A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?"

In other words, "this study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences," Levin says--whether in the rapid arrival of self-driving cars, changing gene drives to wipe out whole lineages of viruses, or the many other complex and autonomous systems that will increasingly shape the human experience.

"There's all of this innate creativity in life," says UVM's Josh Bongard. "We want to understand that more deeply--and how we can direct and push it toward new forms."

###

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Summary

Scientists at the Sloan Kettering Institute have discovered that the ability of cancers to metastasize to other organs is dependent upon their ability to coopt natural wound-healing pathways. The findings provide a new way of looking at metastasis and its possible treatment.

Metastasis the spreading of cancer to other regions in the body is responsible for 90% of cancer deaths. Yet not much is known about what makes cancer cells capable of metastasizing. Now a major study from investigators at the Sloan Kettering Institute concludes that metastasis-initiating cells employ a devilish trick to spread: They co-opt the bodys natural wound-healing abilities.

The new findings, published January 13 in the inaugural issue of the journal Nature Cancer, provide a novel framework for thinking about metastasis and how to treat it.

We now understand metastasis as the regeneration of the wrong tissue the tumor in the wrong place distant vital organs, says Joan Massagu, Director of the Sloan Kettering Institute and the corresponding author on the paper. This is not just a metaphor. It is literally true in molecular and physiological terms.

There were previously clues that cancers might make use of wound-healing pathways to support their growth. Back in the 1980s, researcher Harold Dvorak dubbed tumors wounds that do not heal. But the new findings present the first detailed picture of how this process works on the level of cells and molecules and there are plenty of surprises.

This is not just a metaphor. It is literally true in molecular and physiological terms.

Though metastasis is deadly, its not something that cancer cells can do easily. To spread, cancer cells must successfully detach from their neighbors, break through tissue layers separating them from the circulation, swim or crawl to a new location in the body through blood or lymph fluid, exit these vessels, then take root and start growing in the new location.

At each step in this process, the majority of loose cancer cells die off. Fewer than 1% of all cancer cells shed from a tumor will ultimately form measurable metastases. But those that do will have proven themselves to be unusually hearty.

Once cancer cells learn how to survive the stress of living in a foreign environment, theyre very difficult to get rid of, says Karuna Ganesh, a physician-scientist in the Molecular Pharmacology Program at SKI and the papers first author. They are a completely different entity from the tumor that they started off in. But not, it seems, because they have different mutations.

Dr. Ganesh and her colleagues wanted to understand what enables some cells to survive this stressful journey. They homed in on a molecule called L1CAM, which previous studies from the Massagu lab had shown is necessary for numerous types of cancer cells to successfully metastasize to organs. Normal healthy tissues do not typically make L1CAM, but advanced cancers often do. Exactly what triggers the expression of L1CAM has so far been a mystery.

From looking at human tumor tissues under a microscope, it was clear to the researchers that dividing cells with L1CAM were more common in areas where an epithelial layer was disrupted that is, wounded. This led the scientists to wonder whether L1CAM is required for normal wound repair, such as occurs in the intestine following colitis. Using a mouse model of colitis, they found that indeed this was the case.

Next, they wanted to know exactly what it is about the wounding process that causes cells to switch on L1CAM. To find out, they turned to a recently developed technology called tissue organoids. These three-dimensional structures are grown from human cells and in many ways resemble human organs. Working with MSK colorectal cancer surgeon Julio Garcia-Aguilar, Dr. Ganesh was able to obtain fresh samples of metastatic colorectal tumors, which she then grew in jelly until they formed three-dimensional tumor organoids.

Using these tumor organoids, she and her colleagues were able to show that simply separating cells from their neighbors was enough to trigger L1CAM production. Whats more, the organoids enabled the researchers to work out in detail the molecular signals that switch on L1CAM.

Why would metastasis-initiating cells share a marker of wound healing? Fundamentally, wounds are a breach in the integrity of the epithelial layer of our skin: Cells that are normally linked tightly to each other to form a protective barrier are suddenly separated from their neighbors. Similarly, in metastasis, cells detach from their neighbors and adopt a migratory behavior to reach new locations. The researchers suspect that the wound repair program equips both types of cells to survive this anchorless state. In the first case, it allows cells to move into the breach and make new tissues, which is a good thing; in the second, it enables metastatic cells to detach and colonize new destinations, which is very bad.

Metastasis is wound healing gone wrong, Dr. Ganesh says.

What Is Metastatic Cancer? Answers to Six Common Questions

Learn about MSKs approach to treating cancer that has spread from the original tumor to other parts of the body.

Since previous researchers had linked cancer growth to wound healing, the SKI scientists asked whether cells that produce L1CAM are necessary to initiate the growth of a primary tumor. Using a mouse model, they found somewhat surprisingly that they were not; tumors formed fine without it. However, these L1CAM-making cells were necessary for tumors to metastasize. This led the researchers to conclude that the stem cells that form primary tumors are different from the ones that form metastases.

Scientists are increasingly interested in cancer stem cells the subset of cells within a tumor than can regrow a tumor. A crucial lesson from these findings is that cancer models that rely on the growth of primary tumors are not adequate for understanding metastasis or for testing medicines that might treat it. Thats because the stem cells that generate primary tumors are fundamentally different from those that generate metastases.

The SKI scientists think that this newly identified connection between metastasis-initiating cells and wound healing will open up promising avenues of research. They are currently looking for drugs that might block L1CAM and thereby rob cancer cells of their ability to metastasize. They plan to continue collaborating with MSK colleagues to bring these insights to the patients in the clinic.

There is such astrong translational environment at MSK, Dr. Ganesh adds. Everybody is eager to collaborate on work that might improve outcomes for patients with metastatic cancer.

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What Does Cancer Metastasis Have to Do with Wound Healing? More than You Might Think - On Cancer - Memorial Sloan Kettering

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Poblano peppers (Capsicum annuum) are a type of chili pepper native to Mexico that can add zing to your meals.

Theyre green and resemble other varieties of peppers, but they tend to be larger than jalapeos and smaller than bell peppers.

Fresh poblanos have a mild, slightly sweet flavor, although if they are left to ripen until theyre red, they taste much hotter.

Dried poblano peppers that are fully ripe and deep red are known as ancho chiles, a popular ingredient in mole sauces and other Mexican dishes.

This article provides a complete overview of poblano peppers, including their possible benefits and uses.

Poblanos are low in calories and rich in fiber and several micronutrients.

In fact, 1 cup (118 grams) of chopped raw poblano peppers provides (1):

Poblanos are particularly rich in vitamins A and C. These two nutrients act as antioxidants in your body and help fight underlying damage from free radicals, which may lead to disease (2).

Dried poblano peppers, or ancho chiles, have higher amounts of vitamins A and B2 and other nutrients, compared with fresh poblanos (3).

Poblano peppers are rich in fiber, vitamins A and C, and several other nutrients.

Due to their high amounts of nutrients and beneficial plant compounds, poblano peppers may provide health benefits.

However, there is no substantial research on the health effects of eating poblanos in particular.

Poblanos and other peppers in the Capsicum annuum family are rich in antioxidants, such as vitamin C, capsaicin, and carotenoids, some of which turn into vitamin A in your body (4).

Antioxidants help fight oxidative stress caused by excess free radicals.

Free radicals are reactive molecules that lead to underlying cell damage, which in turn may increase your risk of heart disease, cancer, dementia, and other chronic conditions (5).

Therefore, eating antioxidant-rich poblanos may help prevent illness related to oxidative stress (6, 7).

Capsaicin, a compound in poblanos and other peppers that imparts a spicy taste, may exert anticancer effects.

Specifically, capsaicin may influence genes involved in the spread of cancer and promote cancer cell death, though its role in this process is not fully understood (8).

Test-tube studies suggest that capsaicin may exert anticancer activity against human lung and colorectal cancer cells (9, 10).

However, a review of 10 observational studies in humans found that low capsaicin intake was associated with protection against stomach cancer, while medium-high intake may increase the risk of this disease (11).

More research is needed to fully understand whether eating poblano peppers and other foods with capsaicin has anticancer effects.

Capsaicin may also fight inflammation and help alleviate pain.

Some studies suggest that it binds to nerve cell receptors and, in turn, decreases inflammation and pain (12, 13).

There is limited research on the effects of dietary capsaicin, especially from poblano peppers, on pain. Still, studies in humans and rats suggest that capsaicin supplements may fight inflammation (14, 15).

One study in 376 adults with inflammatory bowel diseases and other gastrointestinal issues found that capsaicin supplements prevented stomach damage (14).

Still, be sure to consult your healthcare provider before taking capsaicin supplements to treat a medical condition.

Poblano peppers are loaded with vitamin C, a water-soluble nutrient thats vital to immune function. Not getting enough vitamin C can lead to an increased risk of developing an infection (16).

Whats more, the capsaicin in poblano peppers has been linked to optimal immune function.

Several animal studies have shown that capsaicin may influence genes involved in the immune response and help protect against autoimmune conditions (17, 18).

While theres no substantial research on the health effects of eating poblanos specifically, studies on the compounds in these peppers suggest that they may have anticancer effects, help fight inflammation, and even boost immunity.

Poblano peppers can be used in a variety of ways.

They can be enjoyed raw in salsas and other dips, as well as added to chilis, taco meat, or sauces.

To prepare a poblano pepper for these dishes, halve the pepper lengthwise, remove the stem and seeds, and then dice it into pieces.

You can also roast poblano peppers whole and then remove the skin, stem, and seeds.

One of the most popular ways to enjoy poblanos is stuffed with ground meat, beans, rice, spices, corn, and tomatoes.

To make stuffed poblanos, halve the peppers, remove the seeds, and roast them in the oven at 350F (177C) for 1015 minutes.

Stuff each pepper half with filling and sprinkle cheese on top, then put them back in the oven for a few more minutes.

You can enjoy poblano peppers in salsas and tacos, or make stuffed poblanos by filling them with meat, beans, tomatoes, corn, and cheese and baking them in the oven.

Poblano peppers are a mild variety of chili peppers that are highly nutritious and equally delicious.

Theyre rich in vitamins A and C, carotenoids, capsaicin, and other compounds that may act as antioxidants, have anticancer activity, and fight inflammation.

Poblano peppers can be added to soups, tacos, or salsas, or stuffed with meat, beans, rice, and cheese.

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Days after shaking hands with German regulators over the launch and coverage of its beta-thalassemia gene therapy, bluebird bio has wooed a Celgene exec to lead its European operations.

Nicola Heffron, a biopharma vet with stints across Eli Lilly, GSK and Shire, jumps from a brief tenure overseeing marketing for Celgenes myeloid portfolio in Summit, NJ. She will now be based in Zug, Switzerland.

Shes replacing Andrew Obenshain as he joins CEO Nick Leschly and the leadership team in Boston, according to Bloomberg, which first reported the news. Obenshains new title is chief of wings.

On Monday bluebird announced that Germany will be the first country to commercially offer Zynteglo, their procedure encoding A-T87Q-globin gene in CD34+ cells extracted from patients. Under their value-based payment scheme, the $1.8 million price is divided into five installments. After an initial payment is made at the time of infusion, the payers wait and see and only pay if the patients continue to be transfusion-free.

Multiple statutory health insurances have signed onto the plan, bluebird said, and University Hospital of Heidelberg will host the first qualified treatment center.

The biotech has been busy sorting out manufacturing specs and talking to individual countries since the EU issued an historic OK last June. Its sanctioned for a specific group of beta-thalassemia patients those who are 12 years and older, transfusion dependent, do not have a 0/0 genotype and for whom hematopoietic stem cell transplantation is appropriate but a donor is not available.

For patients with TDT, lifelong chronic blood transfusions are required in order to survive, bluebird chief commercial officer Alison Finger emphasized in a statement. Their one-time infusion promises to do away with the transfusions for good.

A rolling BLA submission to the FDA has begun, bluebird added.

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Heart problems, graft-versus-host disease are concerns

A new study from Washington University School of Medicine in St. Louis suggests that bone marrow or blood stem cells from healthy donors can harbor extremely rare mutations that can cause health problems for the cancer patients who receive them. Such stem cell transplants are important for treating blood cancers, including acute myeloid leukemia. In the healthy bone marrow pictured, mature red blood cells are shown as small brownish-pink discs; red blood cells that are still developing are in deep blue; and developing white blood cells are in lighter blue.

A stem cell transplant also called a bone marrow transplant is a common treatment for blood cancers, such as acute myeloid leukemia (AML). Such treatment can cure blood cancers but also can lead to life-threatening complications, including heart problems and graft-versus-host disease, in which new immune cells from the donor attack a patients healthy tissues.

A new study from Washington University School of Medicine in St. Louis suggests that extremely rare, harmful genetic mutations present in healthy donors stem cells though not causing health problems in the donors may be passed on to cancer patients receiving stem cell transplants. The intense chemo- and radiation therapy prior to transplant and the immunosuppression given after allow cells with these rare mutations the opportunity to quickly replicate, potentially creating health problems for the patients who receive them, suggests the research, published Jan. 15 in the journal Science Translational Medicine.

Among the concerns are heart damage, graft-versus-host disease and possible new leukemias.

The study, involving samples from patients with AML and their stem cell donors, suggests such rare, harmful mutations are present in surprisingly young donors and can cause problems for recipients even if the mutations are so rare as to be undetectable in the donor by typical genome sequencing techniques. The research opens the door to a larger study that will investigate these rare mutations in many more healthy donors, potentially leading to ways to prevent or mitigate the health effects of such genetic errors in patients receiving stem cell transplants.

There have been suspicions that genetic errors in donor stem cells may be causing problems in cancer patients, but until now we didnt have a way to identify them because they are so rare, said senior author Todd E. Druley, MD, PhD, an associate professor of pediatrics. This study raises concerns that even young, healthy donors blood stem cells may have harmful mutations and provides strong evidence that we need to explore the potential effects of these mutations further.

Added co-author Sima T. Bhatt, MD, an assistant professor of pediatrics who treats pediatric patients with blood cancers at Siteman Kids at St. Louis Childrens Hospital and Washington University School of Medicine: Transplant physicians tend to seek younger donors because we assume this will lead to fewer complications. But we now see evidence that even young and healthy donors can have mutations that will have consequences for our patients. We need to understand what those consequences are if we are to find ways to modify them.

The study analyzed bone marrow from 25 adult patients with AML whose samples had been stored in a repository at Washington University. Samples from their healthy matched donors, who were unrelated to the patients, also were sequenced. The donors samples were provided by the Center for International Blood and Marrow Transplant Research in Milwaukee.

The 25 AML patients were chosen because they each had had samples banked at four separate times: before the transplant, at 30 days post-transplant, at 100 days post-transplant, and one year post-transplant.

Druley co-invented a technique called error-corrected sequencing, to identify extremely rare DNA mutations that would be missed by conventional genome sequencing. Typical next-generation sequencing techniques can correctly identify a mutation that is present in one in 100 cells. The new method, which can distinguish between true mutations and mistakes introduced by the sequencing machine, allows the researchers to find true mutations that are extremely rare those present in as few as one in 10,000 cells.

The healthy donors ranged in age from 20 to 58, with an average age of 26. The researchers sequenced 80 genes known to be associated with AML, and they identified at least one harmful genetic mutation in 11 of the 25 donors, or 44%. They further showed that 84% of all the various mutations identified in the donors samples were potentially harmful, and that 100% of the harmful mutations present in the donors later were found in the recipients. These harmful mutations also persisted over time, and many increased in frequency. Such data suggest the harmful mutations from the donor confer a survival advantage to the cells that harbor them.

We didnt expect this many young, healthy donors to have these types of mutations, Druley said. We also didnt expect 100% of the harmful mutations to be engrafted into the recipients. That was striking.

According to the researchers, the study raises questions about the origins of some of the well-known side effects of stem cell transplantation.

We see a trend between mutations from the donor that persist over time and the development of chronic graft-versus-host disease, said first author Wing Hing Wong, a doctoral student in Druleys lab. We plan to examine this more closely in a larger study.

Though the study was not large enough to establish a causal link, the researchers found that 75% of the patients who received at least one harmful mutation in the 80 genes that persisted over time developed chronic graft-versus-host disease. Among patients who did not receive mutations in the 80 genes, about 50% developed the condition. Because the study was small, this difference was not statistically significant, but it is evidence that the association should be studied more closely. In general, about half of all patients who receive a stem cell transplant go on to develop some form of graft-versus-host disease.

The most common mutation seen in the donors and the cancer patients studied is in a gene associated with heart disease. Healthy people with mutations in this gene are at higher risk of heart attack due to plaque buildup in the arteries.

We know that cardiac dysfunction is a major complication after a bone marrow transplant, but its always been attributed to toxicity from radiation or chemotherapy, Druley said. Its never been linked to mutations in the blood-forming cells. We cant make this claim definitively, but we have data to suggest we should study that in much more detail.

Added Bhatt: Now that weve also linked these mutations to graft-versus-host disease and cardiovascular problems, we have a larger study planned that we hope will answer some of the questions posed by this one.

This work was supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH), grant number R01CA211711; the Hyundai Quantum Award; the Leukemia and Lymphoma Society Scholar Award; the Eli Seth Matthews Leukemia Foundation; and the Kellsies Hope Foundation. The Center for International Blood and Marrow Transplant Research is supported by a Public Health Service Grant/Cooperative Agreement from the NCI, the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID), grant number 5U24CA076518; a Grant/Cooperative Agreement from NHLBI and NCI, grant number 1U24HL138660; a contract with Health Resources and Services Administration (HRSA/DHHS), number HHSH250201700006C; and the Office of Naval Research, grant numbers N00014-17-1-2388, N00014-17-1-2850 and N00014-18-1-2045. Support also was provided by a UKRI future leaders fellowship and by a CRUK Cambridge Centre Early Detection Programme group leader grant.

The Washington University Office of Technology Management has filed a patent application for Ultra-rare Variant Detection from Next-generation Sequencing, which has been licensed by Canopy Biosciences as RareSeq. Druley is a coinventor on this patent. Canopy Biosciences was not involved in the generation of the data presented.

Wong WH, Bhatt S, Trinkaus K, Pusic I, Elliott K, Mahajan N, Wan F, Switzer GE, Confer DL, DiPersio J, Pulsipher MA, Shah NN, Sees J, Bystry A, Blundell JR, Shaw BE, Druley TE. Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation. Science Translational Medicine. Jan. 15, 2020.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Mutations in donors' stem cells may cause problems for cancer patients - Washington University School of Medicine in St. Louis

Cardiac Stem Cells Comments Off on Mutations in donors’ stem cells may cause problems for cancer patients – Washington University School of Medicine in St. Louis | January 16th, 2020

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) announced the launch in Germany of ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene), a one-time gene therapy for patients 12 years and older with transfusion-dependent -thalassemia (TDT) who do not have a 0/0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available. This is the first time ZYNTEGLO is commercially available.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in significantly reduced or absent adult hemoglobin (HbA). In order to survive, people with TDT maintain hemoglobin (Hb) levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload. ZYNTEGLO is a one-time gene therapy that addresses the underlying genetic cause of TDT and offers patients the potential to become transfusion independent, which, once achieved, is expected to be lifelong.

Due to the highly technical and specialized nature of administering gene therapy in rare diseases, bluebird bio is working with institutions that have expertise in stem cell transplant as well as in treating patients with TDT to create qualified treatment centers that will administer ZYNTEGLO. bluebird bio has established a collaboration with University Hospital of Heidelberg as the first qualified treatment center in Germany.

In addition, bluebird has entered into value-based payment agreements with multiple statutory health insurances in Germany to help ensure patients and their healthcare providers have access to ZYNTEGLO and that payers only pay if the therapy delivers on its promise. bluebirds proposed innovative model is limited to five payments made in equal installments. An initial payment is made at the time of infusion. The four additional annual payments are only made if no transfusions for TDT are required for the patient.

For patients with TDT, lifelong chronic blood transfusions are required in order to survive. We are thrilled to announce that ZYNTEGLO will now be available for patients in the EU living with this severe disease, says Alison Finger, chief commercial officer, bluebird bio. In addition to confirming manufacturing readiness of our partner, apceth Biopharma GmbH, bluebird has also submitted a dossier to the Joint Federal Committee (G-BA) in Germany for drug benefit assessment. We would like to thank our collaborators for their commitment in helping us transform the healthcare system by accepting innovative payment models, and we look forward to treating our first commercial patient soon.

About LentiGlobin for -Thalassemia (autologous CD34+ cells encoding A-T87Q-globin gene)

The European Commission granted conditional marketing authorization for LentiGlobin for -thalassemia, to be marketed as ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene) gene therapy, for patients 12 years and older with TDT who do not have a 0/0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

LentiGlobin for -thalassemia adds functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

Non-serious adverse events (AEs) observed during the HGB-204, HGB-207 and HGB-212 clinical studies that were attributed to LentiGlobin for -thalassemia were hot flush, dyspnoea, abdominal pain, pain in extremities, thrombocytopenia, leukopenia, neutropenia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for -thalassemia for TDT.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

The conditional marketing authorization for ZYNTEGLO is valid in the 28 member states of the EU as well as Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration (FDA) granted LentiGlobin for -thalassemia Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT. LentiGlobin for -thalassemia is not approved in the United States.

bluebird bio has initiated the rolling BLA submission for approval in the U.S., and is engaged with the FDA in discussions regarding the requirements and timing of the various components of the rolling BLA submission. Subject to these ongoing discussions, the company is currently planning to complete the BLA submission in the first half of 2020.

LentiGlobin for -thalassemia continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit http://www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207) or NCT03207009 for Northstar-3 (HGB-212).

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for -thalassemia. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of bluebird bio, Inc.

The full common name for ZYNTEGLO: A genetically modified autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced with lentiviral vector encoding the A-T87Q-globin gene.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Companys plans and expectations for the commercialization for ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene, formerly LentiGlobin in TDT) to treat TDT, and the potential implications of clinical data for patients. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that the efficacy and safety results from our prior and ongoing clinical trials of ZYNTEGLO will not continue or be repeated in our ongoing or planned clinical trials of ZYNTEGLO; the risk that the current or planned clinical trials of ZYNTEGLO will be insufficient to support regulatory submissions or marketing approval in the US, or for additional patient populations in the EU; the risk that the production of HbAT87Q may not be sustained over extended periods of time; the risk that we may not secure adequate pricing or reimbursement to support continued development or commercialization of ZYNTEGLO; the risk that our collaborations with qualified treatment centers will not continue or be successful; and that the risk that commercial patients treated with ZYNTEGLO will not achieve or maintain transfusion independence. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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bluebird bio Announces Launch in Germany of ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene) Gene Therapy for Patients 12 Years and Older...

Cardiac Stem Cells Comments Off on bluebird bio Announces Launch in Germany of ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene) Gene Therapy for Patients 12 Years and Older… | January 16th, 2020

The exosomes (or extracellular vesicles) released by stem cells may be the disruptive therapy for tackling age-related diseases doctors and patients have been waiting for. Despite over a decade and a half of hope and hype, stem cell therapy has failed to deliver on the promise.

Stem cell therapy once seemed beguilingly simple. As we age the number of stem cells in our bodies declines and degeneration increases.

The idea back in the early 2000s was that progenitor or adult stem cells (MSCs) could be given to patients as an unmatched (allogeneic) off-the-shelf drug and the administered cells would migrate to sites of damage or disease in the body.

Once there, it was thought, the cells would engraft and persist at these sites of injury and directly replace the patients own damaged cells. The administered cells treating cardiac disease would become a part of the patients heart tissue, for example.

It was thought that by injecting additional stem cells into the body, the new cells would transform the way that we treat certain conditions such as joint pain, stroke and cardiac degeneration. Animal studies and early human trials appeared to bear the idea out.

But nearly 20 years on, the general safety and efficacy of stem cell therapy has still not been proven, experts from the US Food and Drug Administration (FDA) recently concluded in the New England Journal of Medicine.1

Despite the earlier promise, cellular therapy for regenerative medicine is struggling to get approvals and to generate sales. Only a few allogeneic off-the-shelf cellular therapies have been approved for sale worldwide for regenerative medicine, despite huge investments2.

It turned out that a therapy based on transplanting living cells from donors into the patients body was anything but simple.

The first key issue with stem cell therapy is the question mark over safety. Introducing foreign living cells into a system as complex as the human body is challenging.

Predicting the cells behaviour once injected is a problem, FDA experts say.

A growing list of cautionary examples catalogue how things can go wrong when unproven stem cell therapies are used in the clinic; from a kidney failure patient who developed tumours following stem cell therapy, to patients with an age-related eye condition called macular degeneration, who were left blinded by their therapy given at a US clinic3.

In late 2018 and after infections linked to unapproved stem cell treatments sent 12 people to hospital, the FDA issued a stern warning about the cell products4.

Some autologous therapies using the patients own cells have also become notorious in certain countries and the subject of doubtful or dangerous medical tourism.

Today, the only stem cell therapy that has received FDA approval in the regenerative medicine field is the use of blood-forming stem cells for patients with specific blood production disorders.

Stem cells appear to be making little progress toward FDA-approved clinical use. Little wonder, then, that regenerative medicine researchers are increasingly turning to exosomes: packets of beneficial biomolecules released by stem cells.

We now know that the old working hypothesis for how stem cells exert their regenerative effects was wrong. The transplanted stem cells dont stick around long in the recipients body to replace damaged cells; most are cleared within a week.

As researchers from Oxford5 to Scripps6 have now concluded, its the exosomes stem cells release, rather than the cells themselves, that impart the regenerative benefit.

Exosomes are being described as the secret sauce of stem cells. Exosome therapy would avoid all the problems of a therapy based on live stem cells and yet harness a natural regenerative capability from stem cells.

Tellingly, some biotech stocks established back in the early 2000s as stem cell companies have shifted their focus to exosome research.

Exosome drugs could be harvested from stem cells housed in a bioreactor and then purified as a proper drug product to be administered by injection or infusion.

Exosomes should be a simpler, safer, lower cost, more easily stored and transported, alternative to stem cells.

Critically, exosomes are inherently less risky that live stem cell transplants. Exosomes cannot replicate; they cannot transform into malignant cells or other harmful cell types; they are less likely to trigger an immunogenic response; they cannot be infected with virus.

As a further demonstration of their safety, blood plasma contains high concentrations of unmatched exosomes, and blood transfusions have been carried out in hospitals for decades.

And exosomes should have an efficacy advantage, too. Being much smaller than whole cells, exosomes can circulate much more easily through the body to reach sites of injury or disease and trigger healing.

Early academic clinical studies are starting to prove exosomes potential. A recent placebo-controlled trial on 40 patients with advanced chronic kidney disease showed that the patients receiving exosomes saw enhanced kidney function at 12 months after treatment and no adverse events in the treatment group7.

Exosomes administered to patients could exert their regenerative effects in a number of ways giving treatment by exosomes multiple shots at goal.

Some degeneration, such as Parkinsons Disease, is due to a loss of specialised cells over time. Struggling cells that take up exosomes can be rescued from programmed cell death (apoptosis), and restored to health, thanks to the regenerative genetic material and the protein and lipid cellular building blocks that the exosome delivers.

Degeneration with age has also been associated with an increase in senescence cells. Senescent cells are like zombie cells that dont undergo normal clearance, yet cannot divide and proliferate to generate new tissue.

Recent research points to a benefit in animal models of human disease when the number of senescent cells is reduced. In 2019 researchers published that exosomes and vesicles from stem cells can alleviate cellular aging (senescence) in cells exposed to the exosomes/vesicles8.

Exosomes can also play a role in a recently discovered, previously unsuspected regenerative process in our bodies. Exosomes can trigger fully differentiated, specialised cells such as liver cells (hepatocytes) to a de-differentiate into a more stem cell-like state cell type9 and then maintain a pool of progenitor cells that can replenish the damaged liver with new cells10.

This same mechanism could be used to treat cardiac disease (e.g. cardiac ischemia where a lack of blood flow leads to cardiac muscle cell death). Normally a damaged heart fails to regenerate and becomes fibrotic with scar tissue.

Unfortunately, the scar tissue doesnt have the capacity to beat like cardiomyocytes, so increased fibrosis leads to progressive loss of heart pumping ejected volume and impairment or death. But using exosomes to reprogram the patients own heart muscle cells into cardiac progenitor stem cells offers a new way to treat cardiac damage and drive regeneration.

Exosomes from stem cells could be a better medicine than live stem cells a way to harness stem cells regenerative power without all the problems and disappointment.

But while stem cells secrete trillions of exosomes naturally, efficient separation and purification of exosomes has proven to be very difficult indeed11. Until now.

Exopharms proprietary LEAP technology is a robust and reliable method for producing a well-defined set of proprietary pharmaceutical-grade exosome product as a next-generation cell-free regenerative medicine.

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The Next Big Thing: Exosomes versus Stem Cells

Cardiac Stem Cells Comments Off on The Next Big Thing: Exosomes versus Stem Cells | January 14th, 2020

For many years, researchers have been seeking to understand the body's ability to repair and replace the cells and tissues of some organs, but not others. After years of work pursuing the how and why of seemingly indiscriminant cell repair mechanisms, scientists have now focused their attention on adult stem cells. It has long been known that stem cells are capable of renewing themselves and that they can generate multiple cell types. Today, there is new evidence that stem cells are present in far more tissues and organs than once thought and that these cells are capable of developing into more kinds of cells than previously imagined. Efforts are now underway to harness stem cells and to take advantage of this new found capability, with the goal of devising new and more effective treatments for a host of diseases and disabilities. What lies ahead for the use of adult stem cells is unknown, but it is certain that there are many research questions to be answered and that these answers hold great promise for the future.

Adult stem cells, like all stem cells, share at least two characteristics. First, they can make identical copies of themselves for long periods of time; this ability to proliferate is referred to as long-term self-renewal. Second, they can give rise to mature cell types that have characteristic morphologies (shapes) and specialized functions. Typically, stem cells generate an intermediate cell type or types before they achieve their fully differentiated state. The intermediate cell is called a precursor or progenitor cell. Progenitor or precursor cells in fetal or adult tissues are partly differentiated cells that divide and give rise to differentiated cells. Such cells are usually regarded as "committed" to differentiating along a particular cellular development pathway, although this characteristic may not be as definitive as once thought [82] (see Figure 4.1. Distinguishing Features of Progenitor/Precursor Cells and Stem Cells).

Figure 4.1. Distinguishing Features of Progenitor/Precursor Cells and Stem Cells. A stem cell is an unspecialized cell that is capable of replicating or self renewing itself and developing into specialized cells of a variety of cell types. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell. Shown here is an example of a hematopoietic stem cell producing a second generation stem cell and a neuron. A progenitor cell (also known as a precursor cell) is unspecialized or has partial characteristics of a specialized cell that is capable of undergoing cell division and yielding two specialized cells. Shown here is an example of a myeloid progenitor/precursor undergoing cell division to yield two specialized cells (a neutrophil and a red blood cell).

( 2001 Terese Winslow, Lydia Kibiuk)

Adult stem cells are rare. Their primary functions are to maintain the steady state functioning of a cellcalled homeostasisand, with limitations, to replace cells that die because of injury or disease [44, 58]. For example, only an estimated 1 in 10,000 to 15,000 cells in the bone marrow is a hematopoietic (bloodforming) stem cell (HSC) [105]. Furthermore, adult stem cells are dispersed in tissues throughout the mature animal and behave very differently, depending on their local environment. For example, HSCs are constantly being generated in the bone marrow where they differentiate into mature types of blood cells. Indeed, the primary role of HSCs is to replace blood cells [26] (see Chapter 5. Hematopoietic Stem Cells). In contrast, stem cells in the small intestine are stationary, and are physically separated from the mature cell types they generate. Gut epithelial stem cells (or precursors) occur at the bases of cryptsdeep invaginations between the mature, differentiated epithelial cells that line the lumen of the intestine. These epithelial crypt cells divide fairly often, but remain part of the stationary group of cells they generate [93].

Unlike embryonic stem cells, which are defined by their origin (the inner cell mass of the blastocyst), adult stem cells share no such definitive means of characterization. In fact, no one knows the origin of adult stem cells in any mature tissue. Some have proposed that stem cells are somehow set aside during fetal development and restrained from differentiating. Definitions of adult stem cells vary in the scientific literature range from a simple description of the cells to a rigorous set of experimental criteria that must be met before characterizing a particular cell as an adult stem cell. Most of the information about adult stem cells comes from studies of mice. The list of adult tissues reported to contain stem cells is growing and includes bone marrow, peripheral blood, brain, spinal cord, dental pulp, blood vessels, skeletal muscle, epithelia of the skin and digestive system, cornea, retina, liver, and pancreas.

In order to be classified as an adult stem cell, the cell should be capable of self-renewal for the lifetime of the organism. This criterion, although fundamental to the nature of a stem cell, is difficult to prove in vivo. It is nearly impossible, in an organism as complex as a human, to design an experiment that will allow the fate of candidate adult stem cells to be identified in vivo and tracked over an individual's entire lifetime.

Ideally, adult stem cells should also be clonogenic. In other words, a single adult stem cell should be able to generate a line of genetically identical cells, which then gives rise to all the appropriate, differentiated cell types of the tissue in which it resides. Again, this property is difficult to demonstrate in vivo; in practice, scientists show either that a stem cell is clonogenic in vitro, or that a purified population of candidate stem cells can repopulate the tissue.

An adult stem cell should also be able to give rise to fully differentiated cells that have mature phenotypes, are fully integrated into the tissue, and are capable of specialized functions that are appropriate for the tissue. The term phenotype refers to all the observable characteristics of a cell (or organism); its shape (morphology); interactions with other cells and the non-cellular environment (also called the extracellular matrix); proteins that appear on the cell surface (surface markers); and the cell's behavior (e.g., secretion, contraction, synaptic transmission).

The majority of researchers who lay claim to having identified adult stem cells rely on two of these characteristicsappropriate cell morphology, and the demonstration that the resulting, differentiated cell types display surface markers that identify them as belonging to the tissue. Some studies demonstrate that the differentiated cells that are derived from adult stem cells are truly functional, and a few studies show that cells are integrated into the differentiated tissue in vivo and that they interact appropriately with neighboring cells. At present, there is, however, a paucity of research, with a few notable exceptions, in which researchers were able to conduct studies of genetically identical (clonal) stem cells. In order to fully characterize the regenerating and self-renewal capabilities of the adult stem cell, and therefore to truly harness its potential, it will be important to demonstrate that a single adult stem cell can, indeed, generate a line of genetically identical cells, which then gives rise to all the appropriate, differentiated cell types of the tissue in which it resides.

Adult stem cells have been identified in many animal and human tissues. In general, three methods are used to determine whether candidate adult stem cells give rise to specialized cells. Adult stem cells can be labeled in vivo and then they can be tracked. Candidate adult stem cells can also be isolated and labeled and then transplanted back into the organism to determine what becomes of them. Finally, candidate adult stem cells can be isolated, grown in vitro and manipulated, by adding growth factors or introducing genes that help determine what differentiated cells types they will yield. For example, currently, scientists believe that stem cells in the fetal and adult brain divide and give rise to more stem cells or to several types of precursor cells, which give rise to nerve cells (neurons), of which there are many types.

It is often difficultif not impossibleto distinguish adult, tissue-specific stem cells from progenitor cells, which are found in fetal or adult tissues and are partly differentiated cells that divide and give rise to differentiated cells. These are cells found in many organs that are generally thought to be present to replace cells and maintain the integrity of the tissue. Progenitor cells give rise to certain types of cellssuch as the blood cells known as T lymphocytes, B lymphocytes, and natural killer cellsbut are not thought to be capable of developing into all the cell types of a tissue and as such are not truly stem cells. The current wave of excitement over the existence of stem cells in many adult tissues is perhaps fueling claims that progenitor or precursor cells in those tissues are instead stem cells. Thus, there are reports of endothelial progenitor cells, skeletal muscle stem cells, epithelial precursors in the skin and digestive system, as well as some reports of progenitors or stem cells in the pancreas and liver. A detailed summary of some of the evidence for the existence of stem cells in various tissues and organs is presented later in the chapter.

It was not until recently that anyone seriously considered the possibility that stem cells in adult tissues could generate the specialized cell types of another type of tissue from which they normally resideeither a tissue derived from the same embryonic germ layer or from a different germ layer (see Table 1.1. Embryonic Germ Layers From Which Differentiated Tissues Develop). For example, studies have shown that blood stem cells (derived from mesoderm) may be able to generate both skeletal muscle (also derived from mesoderm) and neurons (derived from ectoderm). That realization has been triggered by a flurry of papers reporting that stem cells derived from one adult tissue can change their appearance and assume characteristics that resemble those of differentiated cells from other tissues.

The term plasticity, as used in this report, means that a stem cell from one adult tissue can generate the differentiated cell types of another tissue. At this time, there is no formally accepted name for this phenomenon in the scientific literature. It is variously referred to as "plasticity" [15, 52], "unorthodox differentiation" [10] or "transdifferentiation" [7, 54].

To be able to claim that adult stem cells demonstrate plasticity, it is first important to show that a cell population exists in the starting tissue that has the identifying features of stem cells. Then, it is necessary to show that the adult stem cells give rise to cell types that normally occur in a different tissue. Neither of these criteria is easily met. Simply proving the existence of an adult stem cell population in a differentiated tissue is a laborious process. It requires that the candidate stem cells are shown to be self-renewing, and that they can give rise to the differentiated cell types that are characteristic of that tissue.

To show that the adult stem cells can generate other cell types requires them to be tracked in their new environment, whether it is in vitro or in vivo. In general, this has been accomplished by obtaining the stem cells from a mouse that has been genetically engineered to express a molecular tag in all its cells. It is then necessary to show that the labeled adult stem cells have adopted key structural and biochemical characteristics of the new tissue they are claimed to have generated. Ultimatelyand most importantlyit is necessary to demonstrate that the cells can integrate into their new tissue environment, survive in the tissue, and function like the mature cells of the tissue.

In the experiments reported to date, adult stem cells may assume the characteristics of cells that have developed from the same primary germ layer or a different germ layer (see Figure 4.2. Preliminary Evidence of Plasticity Among Nonhuman Adult Stem Cells). For example, many plasticity experiments involve stem cells derived from bone marrow, which is a mesodermal derivative. The bone marrow stem cells may then differentiate into another mesodermally derived tissue such as skeletal muscle [28, 43], cardiac muscle [51, 71] or liver [4, 54, 97].

Figure 4.2. Preliminary Evidence of Plasticity Among Nonhuman Adult Stem Cells.

( 2001 Terese Winslow, Lydia Kibiuk, Caitlin Duckwall)

Alternatively, adult stem cells may differentiate into a tissue thatduring normal embryonic developmentwould arise from a different germ layer. For example, bone marrow-derived cells may differentiate into neural tissue, which is derived from embryonic ectoderm [15, 65]. Andreciprocallyneural stem cell lines cultured from adult brain tissue may differentiate to form hematopoietic cells [13], or even give rise to many different cell types in a chimeric embryo [17]. In both cases cited above, the cells would be deemed to show plasticity, but in the case of bone marrow stem cells generating brain cells, the finding is less predictable.

In order to study plasticity within and across germ layer lines, the researcher must be sure that he/she is using only one kind of adult stem cell. The vast majority of experiments on plasticity have been conducted with adult stem cells derived either from the bone marrow or the brain. The bone marrow-derived cells are sometimes sortedusing a panel of surface markersinto populations of hematopoietic stem cells or bone marrow stromal cells [46, 54, 71]. The HSCs may be highly purified or partially purified, depending on the conditions used. Another way to separate population of bone marrow cells is by fractionation to yield cells that adhere to a growth substrate (stromal cells) or do not adhere (hematopoietic cells) [28].

To study plasticity of stem cells derived from the brain, the researcher must overcome several problems. Stem cells from the central nervous system (CNS), unlike bone marrow cells, do not occur in a single, accessible location. Instead, they are scattered in three places, at least in rodent brainthe tissue around the lateral ventricles in the forebrain, a migratory pathway for the cells that leads from the ventricles to the olfactory bulbs, and the hippocampus. Many of the experiments with CNS stem cells involve the formation of neurospheres, round aggregates of cells that are sometimes clonally derived. But it is not possible to observe cells in the center of a neurosphere, so to study plasticity in vitro, the cells are usually dissociated and plated in monolayers. To study plasticity in vivo, the cells may be dissociated before injection into the circulatory system of the recipient animal [13], or injected as neurospheres [17].

The differentiated cell types that result from plasticity are usually reported to have the morphological characteristics of the differentiated cells and to display their characteristic surface markers. In reports that transplanted adult stem cells show plasticity in vivo, the stem cells typically are shown to have integrated into a mature host tissue and assumed at least some of its characteristics [15, 28, 51, 65, 71]. Many plasticity experiments involve injury to a particular tissue, which is intended to model a particular human disease or injury [13, 54, 71]. However, there is limited evidence to date that such adult stem cells can generate mature, fully functional cells or that the cells have restored lost function in vivo [54]. Most of the studies that show the plasticity of adult stem cells involve cells that are derived from the bone marrow [15, 28, 54, 65, 77] or brain [13, 17]. To date, adult stem cells are best characterized in these two tissues, which may account for the greater number of plasticity studies based on bone marrow and brain. Collectively, studies on plasticity suggest that stem cell populations in adult mammals are not fixed entities, and that after exposure to a new environment, they may be able to populate other tissues and possibly differentiate into other cell types.

It is not yet possible to say whether plasticity occurs normally in vivo. Some scientists think it may [14, 64], but as yet there is no evidence to prove it. Also, it is not yet clear to what extent plasticity can occur in experimental settings, and howor whetherthe phenomenon can be harnessed to generate tissues that may be useful for therapeutic transplantation. If the phenomenon of plasticity is to be used as a basis for generating tissue for transplantation, the techniques for doing it will need to be reproducible and reliable (see Chapter 10. Assessing Human Stem Cell Safety). In some cases, debate continues about observations that adult stem cells yield cells of tissue types different than those from which they were obtained [7, 68].

More than 30 years ago, Altman and Das showed that two regions of the postnatal rat brain, the hippocampus and the olfactory bulb, contain dividing cells that become neurons [5, 6]. Despite these reports, the prevailing view at the time was that nerve cells in the adult brain do not divide. In fact, the notion that stem cells in the adult brain can generate its three major cell typesastrocytes and oligodendrocytes, as well as neuronswas not accepted until far more recently. Within the past five years, a series of studies has shown that stem cells occur in the adult mammalian brain and that these cells can generate its three major cell lineages [35, 48, 63, 66, 90, 96, 104] (see Chapter 8. Rebuilding the Nervous System with Stem Cells).

Today, scientists believe that stem cells in the fetal and adult brain divide and give rise to more stem cells or to several types of precursor cells. Neuronal precursors (also called neuroblasts) divide and give rise to nerve cells (neurons), of which there are many types. Glial precursors give rise to astrocytes or oligodendrocytes. Astrocytes are a kind of glial cell, which lend both mechanical and metabolic support for neurons; they make up 70 to 80 percent of the cells of the adult brain. Oligodendrocytes make myelin, the fatty material that ensheathes nerve cell axons and speeds nerve transmission. Under normal, in vivo conditions, neuronal precursors do not give rise to glial cells, and glial precursors do not give rise to neurons. In contrast, a fetal or adult CNS (central nervous systemthe brain and spinal cord) stem cell may give rise to neurons, astrocytes, or oligodendrocytes, depending on the signals it receives and its three-dimensional environment within the brain tissue. There is now widespread consensus that the adult mammalian brain does contain stem cells. However, there is no consensus about how many populations of CNS stem cells exist, how they may be related, and how they function in vivo. Because there are no markers currently available to identify the cells in vivo, the only method for testing whether a given population of CNS cells contains stem cells is to isolate the cells and manipulate them in vitro, a process that may change their intrinsic properties [67].

Despite these barriers, three groups of CNS stem cells have been reported to date. All occur in the adult rodent brain and preliminary evidence indicates they also occur in the adult human brain. One group occupies the brain tissue next to the ventricles, regions known as the ventricular zone and the sub-ventricular zone (see discussion below). The ventricles are spaces in the brain filled with cerebrospinal fluid. During fetal development, the tissue adjacent to the ventricles is a prominent region of actively dividing cells. By adulthood, however, this tissue is much smaller, although it still appears to contain stem cells [70].

A second group of adult CNS stem cells, described in mice but not in humans, occurs in a streak of tissue that connects the lateral ventricle and the olfactory bulb, which receives odor signals from the nose. In rodents, olfactory bulb neurons are constantly being replenished via this pathway [59, 61]. A third possible location for stem cells in adult mouse and human brain occurs in the hippocampus, a part of the brain thought to play a role in the formation of certain kinds of memory [27, 34].

Central Nervous System Stem Cells in the Subventricular Zone. CNS stem cells found in the forebrain that surrounds the lateral ventricles are heterogeneous and can be distinguished morphologically. Ependymal cells, which are ciliated, line the ventricles. Adjacent to the ependymal cell layer, in a region sometimes designated as the subependymal or subventricular zone, is a mixed cell population that consists of neuroblasts (immature neurons) that migrate to the olfactory bulb, precursor cells, and astrocytes. Some of the cells divide rapidly, while others divide slowly. The astrocyte-like cells can be identified because they contain glial fibrillary acidic protein (GFAP), whereas the ependymal cells stain positive for nestin, which is regarded as a marker of neural stem cells. Which of these cells best qualifies as a CNS stem cell is a matter of debate [76].

A recent report indicates that the astrocytes that occur in the subventricular zone of the rodent brain act as neural stem cells. The cells with astrocyte markers appear to generate neurons in vivo, as identified by their expression of specific neuronal markers. The in vitro assay to demonstrate that these astrocytes are, in fact, stem cells involves their ability to form neurospheresgroupings of undifferentiated cells that can be dissociated and coaxed to differentiate into neurons or glial cells [25]. Traditionally, these astrocytes have been regarded as differentiated cells, not as stem cells and so their designation as stem cells is not universally accepted.

A series of similar in vitro studies based on the formation of neurospheres was used to identify the subependymal zone as a source of adult rodent CNS stem cells. In these experiments, single, candidate stem cells derived from the subependymal zone are induced to give rise to neurospheres in the presence of mitogenseither epidermal growth factor (EGF) or fibroblast growth factor-2 (FGF-2). The neurospheres are dissociated and passaged. As long as a mitogen is present in the culture medium, the cells continue forming neurospheres without differentiating. Some populations of CNS cells are more responsive to EGF, others to FGF [100]. To induce differentiation into neurons or glia, cells are dissociated from the neurospheres and grown on an adherent surface in serum-free medium that contains specific growth factors. Collectively, the studies demonstrate that a population of cells derived from the adult rodent brain can self-renew and differentiate to yield the three major cell types of the CNS cells [41, 69, 74, 102].

Central Nervous System Stem Cells in the Ventricular Zone. Another group of potential CNS stem cells in the adult rodent brain may consist of the ependymal cells themselves [47]. Ependymal cells, which are ciliated, line the lateral ventricles. They have been described as non-dividing cells [24] that function as part of the blood-brain barrier [22]. The suggestion that ependymal cells from the ventricular zone of the adult rodent CNS may be stem cells is therefore unexpected. However, in a recent study, in which two molecular tagsthe fluorescent marker Dil, and an adenovirus vector carrying lacZ tagswere used to label the ependymal cells that line the entire CNS ventricular system of adult rats, it was shown that these cells could, indeed, act as stem cells. A few days after labeling, fluorescent or lacZ+ cells were observed in the rostral migratory stream (which leads from the lateral ventricle to the olfactory bulb), and then in the olfactory bulb itself. The labeled cells in the olfactory bulb also stained for the neuronal markers III tubulin and Map2, which indicated that ependymal cells from the ventricular zone of the adult rat brain had migrated along the rostral migratory stream to generate olfactory bulb neurons in vivo [47].

To show that Dil+ cells were neural stem cells and could generate astrocytes and oligodendrocytes as well as neurons, a neurosphere assay was performed in vitro. Dil-labeled cells were dissociated from the ventricular system and cultured in the presence of mitogen to generate neurospheres. Most of the neurospheres were Dil+; they could self-renew and generate neurons, astrocytes, and oligodendrocytes when induced to differentiate. Single, Dil+ ependymal cells isolated from the ventricular zone could also generate self-renewing neurospheres and differentiate into neurons and glia.

To show that ependymal cells can also divide in vivo, bromodeoxyuridine (BrdU) was administered in the drinking water to rats for a 2- to 6-week period. Bromodeoxyuridine (BrdU) is a DNA precursor that is only incorporated into dividing cells. Through a series of experiments, it was shown that ependymal cells divide slowly in vivo and give rise to a population of progenitor cells in the subventricular zone [47]. A different pattern of scattered BrdU-labeled cells was observed in the spinal cord, which suggested that ependymal cells along the central canal of the cord occasionally divide and give rise to nearby ependymal cells, but do not migrate away from the canal.

Collectively, the data suggest that CNS ependymal cells in adult rodents can function as stem cells. The cells can self-renew, and most proliferate via asymmetrical division. Many of the CNS ependymal cells are not actively dividing (quiescent), but they can be stimulated to do so in vitro (with mitogens) or in vivo (in response to injury). After injury, the ependymal cells in the spinal cord only give rise to astrocytes, not to neurons. How and whether ependymal cells from the ventricular zone are related to other candidate populations of CNS stem cells, such as those identified in the hippocampus [34], is not known.

Are ventricular and subventricular zone CNS stem cells the same population? These studies and other leave open the question of whether cells that directly line the ventriclesthose in the ventricular zoneor cells that are at least a layer removed from this zonein the subventricular zone are the same population of CNS stem cells. A new study, based on the finding that they express different genes, confirms earlier reports that the ventricular and subventricular zone cell populations are distinct. The new research utilizes a technique called representational difference analysis, together with cDNA microarray analysis, to monitor the patterns of gene expression in the complex tissue of the developing and postnatal mouse brain. The study revealed the expression of a panel of genes known to be important in CNS development, such as L3-PSP (which encodes a phosphoserine phosphatase important in cell signaling), cyclin D2 (a cell cycle gene), and ERCC-1 (which is important in DNA excision repair). All of these genes in the recent study were expressed in cultured neurospheres, as well as the ventricular zone, the subventricular zone, and a brain area outside those germinal zones. This analysis also revealed the expression of novel genes such as A16F10, which is similar to a gene in an embryonic cancer cell line. A16F10 was expressed in neurospheres and at high levels in the subventricular zone, but not significantly in the ventricular zone. Interestingly, several of the genes identified in cultured neurospheres were also expressed in hematopoietic cells, suggesting that neural stem cells and blood-forming cells may share aspects of their genetic programs or signaling systems [38]. This finding may help explain recent reports that CNS stem cells derived from mouse brain can give rise to hematopoietic cells after injection into irradiated mice [13].

Central Nervous System Stem Cells in the Hippocampus. The hippocampus is one of the oldest parts of the cerebral cortex, in evolutionary terms, and is thought to play an important role in certain forms of memory. The region of the hippocampus in which stem cells apparently exist in mouse and human brains is the subgranular zone of the dentate gyrus. In mice, when BrdU is used to label dividing cells in this region, about 50% of the labeled cells differentiate into cells that appear to be dentate gyrus granule neurons, and 15% become glial cells. The rest of the BrdU-labeled cells do not have a recognizable phenotype [90]. Interestingly, many, if not all the BrdU-labeled cells in the adult rodent hippocampus occur next to blood vessels [33].

In the human dentate gyrus, some BrdU-labeled cells express NeuN, neuron-specific enolase, or calbindin, all of which are neuronal markers. The labeled neuron-like cells resemble dentate gyrus granule cells, in terms of their morphology (as they did in mice). Other BrdU-labeled cells express glial fibrillary acidic protein (GFAP) an astrocyte marker. The study involved autopsy material, obtained with family consent, from five cancer patients who had been injected with BrdU dissolved in saline prior to their death for diagnostic purposes. The patients ranged in age from 57 to 72 years. The greatest number of BrdU-labeled cells were identified in the oldest patient, suggesting that new neuron formation in the hippocampus can continue late in life [27].

Fetal Central Nervous System Stem Cells. Not surprisingly, fetal stem cells are numerous in fetal tissues, where they are assumed to play an important role in the expansion and differentiation of all tissues of the developing organism. Depending on the developmental stage of an animal, fetal stem cells and precursor cellswhich arise from stem cellsmay make up the bulk of a tissue. This is certainly true in the brain [48], although it has not been demonstrated experimentally in many tissues.

It may seem obvious that the fetal brain contains stem cells that can generate all the types of neurons in the brain as well as astrocytes and oligodendrocytes, but it was not until fairly recently that the concept was proven experimentally. There has been a long-standing question as to whether or not the same cell type gives rise to both neurons and glia. In studies of the developing rodent brain, it has now been shown that all the major cell types in the fetal brain arise from a common population of progenitor cells [20, 34, 48, 80, 108].

Neural stem cells in the mammalian fetal brain are concentrated in seven major areas: olfactory bulb, ependymal (ventricular) zone of the lateral ventricles (which lie in the forebrain), subventricular zone (next to the ependymal zone), hippocampus, spinal cord, cerebellum (part of the hindbrain), and the cerebral cortex. Their number and pattern of development vary in different species. These cells appear to represent different stem cell populations, rather than a single population of stem cells that is dispersed in multiple sites. The normal development of the brain depends not only on the proliferation and differentiation of these fetal stem cells, but also on a genetically programmed process of selective cell death called apoptosis [76].

Little is known about stem cells in the human fetal brain. In one study, however, investigators derived clonal cell lines from CNS stem cells isolated from the diencephalon and cortex of human fetuses, 10.5 weeks post-conception [103]. The study is unusual, not only because it involves human CNS stem cells obtained from fetal tissue, but also because the cells were used to generate clonal cell lines of CNS stem cells that generated neurons, astrocytes, and oligodendrocytes, as determined on the basis of expressed markers. In a few experiments described as "preliminary," the human CNS stem cells were injected into the brains of immunosuppressed rats where they apparently differentiated into neuron-like cells or glial cells.

In a 1999 study, a serum-free growth medium that included EGF and FGF2 was devised to grow the human fetal CNS stem cells. Although most of the cells died, occasionally, single CNS stem cells survived, divided, and ultimately formed neurospheres after one to two weeks in culture. The neurospheres could be dissociated and individual cells replated. The cells resumed proliferation and formed new neurospheres, thus establishing an in vitro system that (like the system established for mouse CNS neurospheres) could be maintained up to 2 years. Depending on the culture conditions, the cells in the neurospheres could be maintained in an undifferentiated dividing state (in the presence of mitogen), or dissociated and induced to differentiate (after the removal of mitogen and the addition of specific growth factors to the culture medium). The differentiated cells consisted mostly of astrocytes (75%), some neurons (13%) and rare oligodendrocytes (1.2%). The neurons generated under these conditions expressed markers indicating they were GABAergic, [the major type of inhibitory neuron in the mammalian CNS responsive to the amino acid neurotransmitter, gammaaminobutyric acid (GABA)]. However, catecholamine-like cells that express tyrosine hydroxylase (TH, a critical enzyme in the dopamine-synthesis pathway) could be generated, if the culture conditions were altered to include different medium conditioned by a rat glioma line (BB49). Thus, the report indicates that human CNS stem cells obtained from early fetuses can be maintained in vitro for a long time without differentiating, induced to differentiate into the three major lineages of the CNS (and possibly two kinds of neurons, GABAergic and TH-positive), and engraft (in rats) in vivo [103].

Central Nervous System Neural Crest Stem Cells. Neural crest cells differ markedly from fetal or adult neural stem cells. During fetal development, neural crest cells migrate from the sides of the neural tube as it closes. The cells differentiate into a range of tissues, not all of which are part of the nervous system [56, 57, 91]. Neural crest cells form the sympathetic and parasympathetic components of the peripheral nervous system (PNS), including the network of nerves that innervate the heart and the gut, all the sensory ganglia (groups of neurons that occur in pairs along the dorsal surface of the spinal cord), and Schwann cells, which (like oligodendrocytes in the CNS) make myelin in the PNS. The non-neural tissues that arise from the neural crest are diverse. They populate certain hormone-secreting glandsincluding the adrenal medulla and Type I cells in the carotid bodypigment cells of the skin (melanocytes), cartilage and bone in the face and skull, and connective tissue in many parts of the body [76].

Thus, neural crest cells migrate far more extensively than other fetal neural stem cells during development, form mesenchymal tissues, most of which develop from embryonic mesoderm as well as the components of the CNS and PNS which arises from embryonic ectoderm. This close link, in neural crest development, between ectodermally derived tissues and mesodermally derived tissues accounts in part for the interest in neural crest cells as a kind of stem cell. In fact, neural crest cells meet several criteria of stem cells. They can self-renew (at least in the fetus) and can differentiate into multiple cells types, which include cells derived from two of the three embryonic germ layers [76].

Recent studies indicate that neural crest cells persist late into gestation and can be isolated from E14.5 rat sciatic nerve, a peripheral nerve in the hindlimb. The cells incorporate BrdU, indicating that they are dividing in vivo. When transplanted into chick embryos, the rat neural crest cells develop into neurons and glia, an indication of their stem cell-like properties [67]. However, the ability of rat E14.5 neural crest cells taken from sciatic nerve to generate nerve and glial cells in chick is more limited than neural crest cells derived from younger, E10.5 rat embryos. At the earlier stage of development, the neural tube has formed, but neural crest cells have not yet migrated to their final destinations. Neural crest cells from early developmental stages are more sensitive to bone morphogenetic protein 2 (BMP2) signaling, which may help explain their greater differentiation potential [106].

The notion that the bone marrow contains stem cells is not new. One population of bone marrow cells, the hematopoietic stem cells (HSCs), is responsible for forming all of the types of blood cells in the body. HSCs were recognized as a stem cells more than 40 years ago [9, 99]. Bone marrow stromal cellsa mixed cell population that generates bone, cartilage, fat, fibrous connective tissue, and the reticular network that supports blood cell formationwere described shortly after the discovery of HSCs [30, 32, 73]. The mesenchymal stem cells of the bone marrow also give rise to these tissues, and may constitute the same population of cells as the bone marrow stromal cells [78]. Recently, a population of progenitor cells that differentiates into endothelial cells, a type of cell that lines the blood vessels, was isolated from circulating blood [8] and identified as originating in bone marrow [89]. Whether these endothelial progenitor cells, which resemble the angioblasts that give rise to blood vessels during embryonic development, represent a bona fide population of adult bone marrow stem cells remains uncertain. Thus, the bone marrow appears to contain three stem cell populationshematopoietic stem cells, stromal cells, and (possibly) endothelial progenitor cells (see Figure 4.3. Hematopoietic and Stromal Stem Cell Differentiation).

Figure 4.3. Hematopoietic and Stromal Stem Cell Differentiation.

( 2001 Terese Winslow, Lydia Kibiuk)

Two more apparent stem cell types have been reported in circulating blood, but have not been shown to originate from the bone marrow. One population, called pericytes, may be closely related to bone marrow stromal cells, although their origin remains elusive [12]. The second population of blood-born stem cells, which occur in four species of animals testedguinea pigs, mice, rabbits, and humansresemble stromal cells in that they can generate bone and fat [53].

Hematopoietic Stem Cells. Of all the cell types in the body, those that survive for the shortest period of time are blood cells and certain kinds of epithelial cells. For example, red blood cells (erythrocytes), which lack a nucleus, live for approximately 120 days in the bloodstream. The life of an animal literally depends on the ability of these and other blood cells to be replenished continuously. This replenishment process occurs largely in the bone marrow, where HSCs reside, divide, and differentiate into all the blood cell types. Both HSCs and differentiated blood cells cycle from the bone marrow to the blood and back again, under the influence of a barrage of secreted factors that regulate cell proliferation, differentiation, and migration (see Chapter 5. Hematopoietic Stem Cells).

HSCs can reconstitute the hematopoietic system of mice that have been subjected to lethal doses of radiation to destroy their own hematopoietic systems. This test, the rescue of lethally irradiated mice, has become a standard by which other candidate stem cells are measured because it shows, without question, that HSCs can regenerate an entire tissue systemin this case, the blood [9, 99]. HSCs were first proven to be blood-forming stem cells in a series of experiments in mice; similar blood-forming stem cells occur in humans. HSCs are defined by their ability to self-renew and to give rise to all the kinds of blood cells in the body. This means that a single HSC is capable of regenerating the entire hematopoietic system, although this has been demonstrated only a few times in mice [72].

Over the years, many combinations of surface markers have been used to identify, isolate, and purify HSCs derived from bone marrow and blood. Undifferentiated HSCs and hematopoietic progenitor cells express c-kit, CD34, and H-2K. These cells usually lack the lineage marker Lin, or express it at very low levels (Lin-/low). And for transplant purposes, cells that are CD34+ Thy1+ Lin- are most likely to contain stem cells and result in engraftment.

Two kinds of HSCs have been defined. Long-term HSCs proliferate for the lifetime of an animal. In young adult mice, an estimated 8 to 10 % of long-term HSCs enter the cell cycle and divide each day. Short-term HSCs proliferate for a limited time, possibly a few months. Long-term HSCs have high levels of telomerase activity. Telomerase is an enzyme that helps maintain the length of the ends of chromosomes, called telomeres, by adding on nucleotides. Active telomerase is a characteristic of undifferentiated, dividing cells and cancer cells. Differentiated, human somatic cells do not show telomerase activity. In adult humans, HSCs occur in the bone marrow, blood, liver, and spleen, but are extremely rare in any of these tissues. In mice, only 1 in 10,000 to 15,000 bone marrow cells is a long-term HSC [105].

Short-term HSCs differentiate into lymphoid and myeloid precursors, the two classes of precursors for the two major lineages of blood cells. Lymphoid precursors differentiate into T cells, B cells, and natural killer cells. The mechanisms and pathways that lead to their differentiation are still being investigated [1, 2]. Myeloid precursors differentiate into monocytes and macrophages, neutrophils, eosinophils, basophils, megakaryocytes, and erythrocytes [3]. In vivo, bone marrow HSCs differentiate into mature, specialized blood cells that cycle constantly from the bone marrow to the blood, and back to the bone marrow [26]. A recent study showed that short-term HSCs are a heterogeneous population that differ significantly in terms of their ability to self-renew and repopulate the hematopoietic system [42].

Attempts to induce HSC to proliferate in vitroon many substrates, including those intended to mimic conditions in the stromahave frustrated scientists for many years. Although HSCs proliferate readily in vivo, they usually differentiate or die in vitro [26]. Thus, much of the research on HSCs has been focused on understanding the factors, cell-cell interactions, and cell-matrix interactions that control their proliferation and differentiation in vivo, with the hope that similar conditions could be replicated in vitro. Many of the soluble factors that regulate HSC differentiation in vivo are cytokines, which are made by different cell types and are then concentrated in the bone marrow by the extracellular matrix of stromal cellsthe sites of blood formation [45, 107]. Two of the most-studied cytokines are granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) [40, 81].

Also important to HSC proliferation and differentiation are interactions of the cells with adhesion molecules in the extracellular matrix of the bone marrow stroma [83, 101, 110].

Bone Marrow Stromal Cells. Bone marrow (BM) stromal cells have long been recognized for playing an important role in the differentiation of mature blood cells from HSCs (see Figure 4.3. Hematopoietic and Stromal Stem Cell Differentiation). But stromal cells also have other important functions [30, 31]. In addition to providing the physical environment in which HSCs differentiate, BM stromal cells generate cartilage, bone, and fat. Whether stromal cells are best classified as stem cells or progenitor cells for these tissues is still in question. There is also a question as to whether BM stromal cells and so-called mesenchymal stem cells are the same population [78].

BM stromal cells have many features that distinguish them from HSCs. The two cell types are easy to separate in vitro. When bone marrow is dissociated, and the mixture of cells it contains is plated at low density, the stromal cells adhere to the surface of the culture dish, and the HSCs do not. Given specific in vitro conditions, BM stromal cells form colonies from a single cell called the colony forming unit-F (CFU-F). These colonies may then differentiate as adipocytes or myelosupportive stroma, a clonal assay that indicates the stem cell-like nature of stromal cells. Unlike HSCs, which do not divide in vitro (or proliferate only to a limited extent), BM stromal cells can proliferate for up to 35 population doublings in vitro [16]. They grow rapidly under the influence of such mitogens as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1) [12].

To date, it has not been possible to isolate a population of pure stromal cells from bone marrow. Panels of markers used to identify the cells include receptors for certain cytokines (interleukin-1, 3, 4, 6, and 7) receptors for proteins in the extracellular matrix, (ICAM-1 and 2, VCAM-1, the alpha-1, 2, and 3 integrins, and the beta-1, 2, 3 and 4 integrins), etc. [64]. Despite the use of these markers and another stromal cell marker called Stro-1, the origin and specific identity of stromal cells have remained elusive. Like HSCs, BM stromal cells arise from embryonic mesoderm during development, although no specific precursor or stem cell for stromal cells has been isolated and identified. One theory about their origin is that a common kind of progenitor cellperhaps a primordial endothelial cell that lines embryonic blood vesselsgives rise to both HSCs and to mesodermal precursors. The latter may then differentiate into myogenic precursors (the satellite cells that are thought to function as stem cells in skeletal muscle), and the BM stromal cells [10].

In vivo, the differentiation of stromal cells into fat and bone is not straightforward. Bone marrow adipocytes and myelosupportive stromal cellsboth of which are derived from BM stromal cellsmay be regarded as interchangeable phenotypes [10, 11]. Adipocytes do not develop until postnatal life, as the bones enlarge and the marrow space increases to accommodate enhanced hematopoiesis. When the skeleton stops growing, and the mass of HSCs decreases in a normal, age-dependent fashion, BM stromal cells differentiate into adipocytes, which fill the extra space. New bone formation is obviously greater during skeletal growth, although bone "turns over" throughout life. Bone forming cells are osteoblasts, but their relationship to BM stromal cells is not clear. New trabecular bone, which is the inner region of bone next to the marrow, could logically develop from the action of BM stromal cells. But the outside surface of bone also turns over, as does bone next to the Haversian system (small canals that form concentric rings within bone). And neither of these surfaces is in contact with BM stromal cells [10, 11].

It is often difficultif not impossibleto distinguish adult, tissue-specific stem cells from progenitor cells. With that caveat in mind, the following summary identifies reports of stem cells in various adult tissues.

Endothelial Progenitor Cells. Endothelial cells line the inner surfaces of blood vessels throughout the body, and it has been difficult to identify specific endothelial stem cells in either the embryonic or the adult mammal. During embryonic development, just after gastrulation, a kind of cell called the hemangioblast, which is derived from mesoderm, is presumed to be the precursor of both the hematopoietic and endothelial cell lineages. The embryonic vasculature formed at this stage is transient and consists of blood islands in the yolk sac. But hemangioblasts, per se, have not been isolated from the embryo and their existence remains in question. The process of forming new blood vessels in the embryo is called vasculogenesis. In the adult, the process of forming blood vessels from pre-existing blood vessels is called angiogenesis [50].

Evidence that hemangioblasts do exist comes from studies of mouse embryonic stem cells that are directed to differentiate in vitro. These studies have shown that a precursor cell derived from mouse ES cells that express Flk-1 [the receptor for vascular endothelial growth factor (VEGF) in mice] can give rise to both blood cells and blood vessel cells [88, 109]. Both VEGF and fibroblast growth factor-2 (FGF-2) play critical roles in endothelial cell differentiation in vivo [79].

Several recent reports indicate that the bone marrow contains cells that can give rise to new blood vessels in tissues that are ischemic (damaged due to the deprivation of blood and oxygen) [8, 29, 49, 94]. But it is unclear from these studies what cell type(s) in the bone marrow induced angiogenesis. In a study which sought to address that question, researchers found that adult human bone marrow contains cells that resemble embryonic hemangioblasts, and may therefore be called endothelial stem cells.

In more recent experiments, human bone marrow-derived cells were injected into the tail veins of rats with induced cardiac ischemia. The human cells migrated to the rat heart where they generated new blood vessels in the infarcted muscle (a process akin to vasculogenesis), and also induced angiogenesis. The candidate endothelial stem cells are CD34+(a marker for HSCs), and they express the transcription factor GATA-2 [51]. A similar study using transgenic mice that express the gene for enhanced green fluorescent protein (which allows the cells to be tracked), showed that bone-marrow-derived cells could repopulate an area of infarcted heart muscle in mice, and generate not only blood vessels, but also cardiomyocytes that integrated into the host tissue [71] (see Chapter 9. Can Stem Cells Repair a Damaged Heart?).

And, in a series of experiments in adult mammals, progenitor endothelial cells were isolated from peripheral blood (of mice and humans) by using antibodies against CD34 and Flk-1, the receptor for VEGF. The cells were mononuclear blood cells (meaning they have a nucleus) and are referred to as MBCD34+ cells and MBFlk1+ cells. When plated in tissue-culture dishes, the cells attached to the substrate, became spindle-shaped, and formed tube-like structures that resemble blood vessels. When transplanted into mice of the same species (autologous transplants) with induced ischemia in one limb, the MBCD34+ cells promoted the formation of new blood vessels [8]. Although the adult MBCD34+ and MBFlk1+ cells function in some ways like stem cells, they are usually regarded as progenitor cells.

Skeletal Muscle Stem Cells. Skeletal muscle, like the cardiac muscle of the heart and the smooth muscle in the walls of blood vessels, the digestive system, and the respiratory system, is derived from embryonic mesoderm. To date, at least three populations of skeletal muscle stem cells have been identified: satellite cells, cells in the wall of the dorsal aorta, and so-called "side population" cells.

Satellite cells in skeletal muscle were identified 40 years ago in frogs by electron microscopy [62], and thereafter in mammals [84]. Satellite cells occur on the surface of the basal lamina of a mature muscle cell, or myofiber. In adult mammals, satellite cells mediate muscle growth [85]. Although satellite cells are normally non-dividing, they can be triggered to proliferate as a result of injury, or weight-bearing exercise. Under either of these circumstances, muscle satellite cells give rise to myogenic precursor cells, which then differentiate into the myofibrils that typify skeletal muscle. A group of transcription factors called myogenic regulatory factors (MRFs) play important roles in these differentiation events. The so-called primary MRFs, MyoD and Myf5, help regulate myoblast formation during embryogenesis. The secondary MRFs, myogenin and MRF4, regulate the terminal differentiation of myofibrils [86].

With regard to satellite cells, scientists have been addressing two questions. Are skeletal muscle satellite cells true adult stem cells or are they instead precursor cells? Are satellite cells the only cell type that can regenerate skeletal muscle. For example, a recent report indicates that muscle stem cells may also occur in the dorsal aorta of mouse embryos, and constitute a cell type that gives rise both to muscle satellite cells and endothelial cells. Whether the dorsal aorta cells meet the criteria of a self-renewing muscle stem cell is a matter of debate [21].

Another report indicates that a different kind of stem cell, called an SP cell, can also regenerate skeletal muscle may be present in muscle and bone marrow. SP stands for a side population of cells that can be separated by fluorescence-activated cell sorting analysis. Intravenously injecting these muscle-derived stem cells restored the expression of dystrophin in mdx mice. Dystrophin is the protein that is defective in people with Duchenne's muscular dystrophy; mdx mice provide a model for the human disease. Dystrophin expression in the SP cell-treated mice was lower than would be needed for clinical benefit. Injection of bone marrow- or muscle-derived SP cells into the dystrophic muscle of the mice yielded equivocal results that the transplanted cells had integrated into the host tissue. The authors conclude that a similar population of SP stem cells can be derived from either adult mouse bone marrow or skeletal muscle, and suggest "there may be some direct relationship between bone marrow-derived stem cells and other tissue- or organ-specific cells" [43]. Thus, stem cell or progenitor cell types from various mesodermally-derived tissues may be able to generate skeletal muscle.

Epithelial Cell Precursors in the Skin and Digestive System. Epithelial cells, which constitute 60 percent of the differentiated cells in the body are responsible for covering the internal and external surfaces of the body, including the lining of vessels and other cavities. The epithelial cells in skin and the digestive tract are replaced constantly. Other epithelial cell populationsin the ducts of the liver or pancreas, for exampleturn over more slowly. The cell population that renews the epithelium of the small intestine occurs in the intestinal crypts, deep invaginations in the lining of the gut. The crypt cells are often regarded as stem cells; one of them can give rise to an organized cluster of cells called a structural-proliferative unit [93].

The skin of mammals contains at least three populations of epithelial cells: epidermal cells, hair follicle cells, and glandular epithelial cells, such as those that make up the sweat glands. The replacement patterns for epithelial cells in these three compartments differ, and in all the compartments, a stem cell population has been postulated. For example, stem cells in the bulge region of the hair follicle appear to give rise to multiple cell types. Their progeny can migrate down to the base of the follicle where they become matrix cells, which may then give rise to different cell types in the hair follicle, of which there are seven [39]. The bulge stem cells of the follicle may also give rise to the epidermis of the skin [95].

Another population of stem cells in skin occurs in the basal layer of the epidermis. These stem cells proliferate in the basal region, and then differentiate as they move toward the outer surface of the skin. The keratinocytes in the outermost layer lack nuclei and act as a protective barrier. A dividing skin stem cell can divide asymmetrically to produce two kinds of daughter cells. One is another self-renewing stem cell. The second kind of daughter cell is an intermediate precursor cell which is then committed to replicate a few times before differentiating into keratinocytes. Self-renewing stem cells can be distinguished from this intermediate precusor cell by their higher level of 1 integrin expression, which signals keratinocytes to proliferate via a mitogen-activated protein (MAP) kinase [112]. Other signaling pathways include that triggered by -catenin, which helps maintain the stem-cell state [111], and the pathway regulated by the oncoprotein c-Myc, which triggers stem cells to give rise to transit amplifying cells [36].

Stem Cells in the Pancreas and Liver. The status of stem cells in the adult pancreas and liver is unclear. During embryonic development, both tissues arise from endoderm. A recent study indicates that a single precursor cell derived from embryonic endoderm may generate both the ventral pancreas and the liver [23]. In adult mammals, however, both the pancreas and the liver contain multiple kinds of differentiated cells that may be repopulated or regenerated by multiple types of stem cells. In the pancreas, endocrine (hormone-producing) cells occur in the islets of Langerhans. They include the beta cells (which produce insulin), the alpha cells (which secrete glucagon), and cells that release the peptide hormones somatostatin and pancreatic polypeptide. Stem cells in the adult pancreas are postulated to occur in the pancreatic ducts or in the islets themselves. Several recent reports indicate that stem cells that express nestinwhich is usually regarded as a marker of neural stem cellscan generate all of the cell types in the islets [60, 113] (see Chapter 7. Stem Cells and Diabetes).

The identity of stem cells that can repopulate the liver of adult mammals is also in question. Recent studies in rodents indicate that HSCs (derived from mesoderm) may be able to home to liver after it is damaged, and demonstrate plasticity in becoming into hepatocytes (usually derived from endoderm) [54, 77, 97]. But the question remains as to whether cells from the bone marrow normally generate hepatocytes in vivo. It is not known whether this kind of plasticity occurs without severe damage to the liver or whether HSCs from the bone marrow generate oval cells of the liver [18]. Although hepatic oval cells exist in the liver, it is not clear whether they actually generate new hepatocytes [87, 98]. Oval cells may arise from the portal tracts in liver and may give rise to either hepatocytes [19, 55] and to the epithelium of the bile ducts [37, 92]. Indeed, hepatocytes themselves, may be responsible for the well-know regenerative capacity of liver.

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German racing driver, Formula 1 Michael Schumacher was hospitalized in one of medical institutions of Paris for the holding of special procedures, namely therapy using stem cells. According to the wife of a holder of numerous records, her husband decided not to disseminate information about their own health, but the woman said that the former athlete is in good hands.

In early autumn last year Michael Schumacher was taken to Hopital Europeen Georges Pompidou, located in Paris, it was said that seven-time world champion was conscious. The athlete was placed in the division of cardiovascular surgery, and to fight for the health of Schumacher took 69-year-old Professor and renowned cardiac surgeon Phillip Menashe, the first at the time transplantiversary patients muscle stem cells from human myocardial infarction.

According to preliminary reports, Schumacher is in the hospital plan to treat the nervous system, but doctors doubt the effectiveness of stem cell therapy to regenerate its functioning. While these experiments have not brought positive results over the last thirty years, writes the Express.

Natasha Kumar is a general assignment reporter at the Times Hub. She has covered sports, entertainment and many other beats in her journalism career, and has lived in Manhattan for more than 8 years. Natasha has appeared periodically on national television shows and has been published in (among others) Hindustan Times.? Times of India

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New Japanese Patent Further Strengthens Intellectual Property Portfolio Covering Companys Novel Platform for Precisely Controlling Core Cell Migration Mechanisms

Decelerator Technology Serves as Key Complement to Companys Cell Motility Accelerator Platform for Enhanced Tissue Repair

NEW YORK, Jan. 14, 2020 (GLOBE NEWSWIRE) -- MicroCures, a biopharmaceutical company developing novel therapeutics that harness the bodys innate regenerative mechanisms to accelerate tissue repair, today announced the issuance of a new Japanese patent providing broad protection for the companys first-of-its-kind cell movement decelerator technology, which has potential therapeutic applications in combating cancer metastases and fibrosis. The companys decelerator technology is being developed alongside MicroCures accelerator technology, which is designed to enhance recovery after trauma. With the newly issued Japanese patent (#6562906), the companys global patent estate now includes eight issued and eight pending patents covering its underlying technology, as well as the therapeutic programs that have emerged from the platform.

MicroCures technology is based on foundational scientific research at Albert Einstein College of Medicine. The company has shown that complex and dynamic networks of microtubules within cells crucially control cell migration, and that this cell movement can be reliably modulated to achieve a range of therapeutic benefits. Based on these findings, the company has established a first-of-its-kind proprietary platform to create siRNA-based therapeutics capable of precisely controlling the speed and direction of cell movement by selectively silencing microtubule regulatory proteins (MRPs).

The company has developed a broad pipeline of therapeutic programs with an initial focus in the area of tissue, nerve and organ repair. Unlike regenerative medicine approaches that rely upon engineered materials or systemic growth factor/stem cell therapeutics, MicroCures accelerator technology directs and enhances the bodys inherent healing processes through local, temporary modulation of cell motility. Additionally, the company is developing a decelerator technology based on the same foundational science. Instead of accelerating cell movement for therapeutic repair and regeneration, this technology is designed to slow or halt the movement of cells, potentially offering a unique, natural approach to preventing cancer metastases and fibrosis.

We have been diligent in building a strong and extensive intellectual property portfolio around our pioneering work focused on precisely controlling core cell migration mechanisms to achieve targeted therapeutic outcomes. This newly issued Japanese patent represents the latest layer of protection for our novel therapeutic platform and the broad pipeline of therapeutic programs that have emerged from it, said Derek Proudian, co-founder and chief executive officer of MicroCures. Not only does this patent portfolio position MicroCures as the industry leader in therapeutic modulation of cell movement, it also opens the company up to a broad range of partnering and licensing opportunities with life science companies of all types.

About MicroCures

MicroCures develops biopharmaceuticals that harness innate cellular mechanisms within the body to precisely control the rate and direction of cell migration, offering the potential to deliver powerful therapeutic benefits for a variety of large and underserved medical applications.

MicroCures has developed a broad pipeline of novel therapeutic programs with an initial focus in the area of tissue, nerve and organ repair. The companys lead therapeutic candidate, siFi2, targets excisional wound healing, a multi-billion dollar market inadequately served by current treatments. Additional applications for the companys cell migration accelerator technology include dermal burn repair, corneal burn repair, cavernous nerve regeneration, spinal cord regeneration, and cardiac tissue repair. Cell migration decelerator applications include combatting cancer metastases and fibrosis. The company protects its unique platform and proprietary therapeutic programs with a robust intellectual property portfolio including eight issued or allowed patents, as well as eight pending patent applications.

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For more information please visit: http://www.microcures.com

Contact:Vida Strategic Partners (On behalf of MicroCures)

Stephanie Diaz (investors)415-675-7401sdiaz@vidasp.com

Tim Brons (media)415-675-7402 tbrons@vidasp.com

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MicroCures Announces Issuance of New Patent Covering First-of-its-Kind Cell Movement Decelerator Technology with Potential Applications in Oncology...

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