It sounds like science fiction: with a light zap of electricity, a tiny stamp-like device transforms your skin cells into reservoirs of blood vessels or brain cells, ready to heal you from within.

Recently, a team of medical mavericks at the Ohio State University introduced a device that does just that. The technology, dubbed tissue nanotransfection (TNT), is set to blow up the field of organ regeneration.

When zapped with a light electrical jolt, the device shoots extra bits of DNA code from its nanotube arrays directly into tiny pores in the skin. There, the DNA triggers the cells to shed their identity and reprograms them into other cell types that can be harvested to repair damaged organs.

Remarkably, the effect spreads with time. The rebooted cells release tiny membrane bubbles onto their neighboring skin cells, coaxing them to undergo transformation. Like zombies, but for good.

So far, the device has already been used to generate neurons to protect the brains of mice with experimental stroke. The team also successfully healed the legs of injured mice by turning the skin cells on their hind limbs into a forest of blood vessels.

While still a ways from human use, scientists believe future iterations of the technology could perform a myriad of medical wonders: repairing damaged organs, relieving brain degeneration, or even restoring aged tissue back to a youthful state.

By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining, says lead author Dr. Chandan Sen, who published the result in Nature Nanotechnology.

In my lab, we have ongoing research trying to understand the mechanism and do even better, adds Dr. L. James Lee, who co-led the study with Sen. So, this is the beginning, more to come.

The Ohio teams research builds on an age-old idea in regenerative medicine: that even aged bodies have the ability to produce and integrate healthy, youthful cellsgiven the right set of cues.

While some controversy remains on whether replacement cells survive in an injured body, scientistsand some rather dubious clinicsare readily exploring the potential of cell-based therapies.

All cells harbor the same set of DNA; whether they turn into heart cells, neurons, or back into stem cells depend on which genes are activated. The gatekeeper of gene expression is a set of specialized proteins. Scientists can stick the DNA code for these proteins into cells, where they hijack its DNA machinery with orders to produce the protein switchesand the cell transforms into another cell type.

The actual process works like this: scientists harvest mature cells from patients, reprogram them into stem cells inside a Petri dish, inject those cells back into the patients and wait for them to develop into the needed cell types.

Its a cumbersome process packed with landmines. Researchers often use viruses to deliver the genetic payload into cells. In some animal studies, this has led to unwanted mutations and cancer. Its also unclear whether the reprogrammed stem cells survive inside the patients. Whether they actually turn into healthy tissue is even more up for debate.

The Ohio teams device tackles many of these problems head on.

Eschewing the need for viruses, the team manufactured a stamp-sized device out of silicon that serves as a reservoir and injector for DNA. Microetched onto each device are arrays of nanochannels that connect to microscopic dents. Scientists can load DNA material into these tiny holding spots, where they sit stably until a ten-millisecond zap shoots them into the recipients tissue.

We based TNT on a bulk transfection, which is often used in the lab to deliver genes into cells, the authors explain. Like its bulk counterpart, the electrical zap opens up tiny, transient pores on the cell membrane, which allows the DNA instructions to get it.

The problem with bulk transfection is that not all genes get into each cell. Some cells may get more than they bargained for and take up more than one copy, which increases the chance of random mutations.

We found that TNT is extremely focused, with each cell receiving ample DNA, the authors say.

The device also skips an intermediary step in cell conversion: rather than turning cells back into stem cells, the team pushed mouse skin cells directly into other mature cell types using different sets of previously-discovered protein factors.

In one early experiment, the team successfully generated neurons from skin cells that seem indistinguishable from their natural counterparts: they shot off electrical pulses and had similar gene expression profiles.

Surprisingly, the team found that even non-zapped cells in the skins deeper layers transformed. Further testing found that the newly reprogrammed neurons released tiny fatty bubbles that contained the molecular instructions for transformation.

When the team harvested these bubbles and injected them into mice subjected to experimental stroke, the bubbles triggered the brain to generate new neurons and repair itself.

We dont know if the bubbles are somehow transforming other brain cell types into neurons, but they do seem to be loaded with molecules that protect the brain, the researchers say.

In an ultimate test of the devices healing potential, the researchers placed it onto the injured hind leg of a handful of mice. Three days prior, their leg arteries had been experimentally severed, whichwhen left untreatedleads to tissue decay.

The team loaded the device with factors that convert skin cells into blood vessel cells. Within a week of conversion, the team watched as new blood vessels sprouted and grew beyond the local treatment area. In the end, TNT-zapped mice had fewer signs of tissue injury and higher leg muscle metabolism compared to non-treated controls.

This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time, says Sen.

A major draw of the device is that its one-touch-and-go.

There are no expensive cell isolation procedures and no finicky lab manipulations. The conversion happens right on the skin, essentially transforming patients bodies into their own prolific bioreactors.

This process only takes less than a second and is non-invasive, and then youre off. The chip does not stay with you, and the reprogramming of the cell starts,says Sen.

Because the converted cells come directly from the patient, theyre in an immune-privileged position, which reduces the chance of rejection.

This means that in the future, if the technology is used to manufacture organs immune suppression is not necessary, says Sen.

While the team plans to test the device in humans as early as next year, Sen acknowledges that theyll likely run into problems.

For one, because the device needs to be in direct contact with tissue, the skin is the only easily-accessible body part to do these conversions. Repairing deeper tissue would require surgery to insert the device into wounded areas. And to many, growing other organ cell types is a pretty creepy thought, especially because the transformation isnt completely localnon-targeted cells are also reprogrammed.

That could be because the body is trying to heal itself, the authors hypothesize. Using the chip on healthy legs didnt sprout new blood vessels, suggesting that the widespread conversion is because of injury, though (for now) there isnt much evidence supporting the idea.

For another, scientists are still working out the specialized factors required to directly convert between cell types. So far, theyve only had limited success.

But Sen and his team are optimistic.

When these things come out for the first time, its basically crossing the chasm from impossible to possible, he says. We have established feasibility.

Image Credit: Researchers demonstrate tissue nanotransfection,courtesy of The Ohio State University Wexner Medical Center.

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This Chip Uses Electricity to Reprogram Cells for Healing - Singularity Hub

Skin Stem Cells Comments Off on This Chip Uses Electricity to Reprogram Cells for Healing – Singularity Hub | August 22nd, 2017

In 2013, University of Virginia researcher Michael McConnell published research that would forever change how scientists study brain cells.

McConnell and a team of nationwide collaborators discovered a genetic mosaic in the brains neurons, proving that brain cells are not exact replicas of each other, and that each individual neuron contains a slightly different genetic makeup.

McConnell, an assistant professor in the School of Medicines Department of Biochemistry and Molecular Genetics, has been using this new information to investigate how variations in individual neurons impact neuropsychiatric disorders like schizophrenia and epilepsy. With a recent $50,000 grant from the Bow Foundation, McConnell will expand his research to explore the cause of a rare genetic disorder known as GNAO1 so named for the faulty protein-coding gene that is its likely source.

GNAO1 causes seizures, movement disorders and developmental delays. Currently, only 50 people worldwide are known to have the disease. The Bow Foundation seeks to increase awareness so that other probable victims of the disorder can be properly diagnosed and to raise funds for further research and treatment.

UVA Today recently sat down with McConnell to find out more about how GNAO1 fits into his broader research and what his continued work means for all neuropsychiatric disorders.

Q. Can you explain the general goals of your lab?

A. My lab has two general directions. One is brain somatic mosaicism, which is a finding that different neurons in the brain have different genomes from one another. We usually think every cell in a single persons body has the same blueprint for how they develop and what they become. It turns out that blueprint changes a little bit in the neurons from neuron to neuron. So you have slightly different versions of the same blueprint and we want to know what that means.

The second area of our work focuses on a new technology called induced pluripotent stem cells, or iPSCs. The technology permits us to make stem cell from skin cells. We can do this with patients, and use the stem cells to make specific cell types with same genetic mutations that are in the patients. That lets us create and study the persons brain cells in a dish. So now, if that person has a neurological disease, we can in a dish study that persons disease and identify drugs that alter the disease. Its a very personalized medicine approach to that disease.

Q. Does cell-level genomic variety exist in other areas of the body outside the central nervous system?

A. Every cell in your body has mutations of one kind or another, but brain cells are there for your whole life, so the differences have a bigger impact there. A skin cell is gone in a month. An intestinal cell is gone in a week. Any changes in those cells will rarely have an opportunity to cause a problem unless they cause a tumor.

Q. How does your research intersect with the goals of the Bow Foundation?

A. Let me back up to a little bit of history on that. When I got to UVA four years ago, I started talking quite a lot with Howard Goodkin and Mark Beenhakker. Mark is an assistant professor in pharmacology. Howard is a pediatric neurologist and works with children with epilepsy. I had this interest in epilepsy and UVA has a historic and current strength in epilepsy research.

We started talking about how to use iPSCs the technology that we use to study mosaicism to help Howards patients. As we talked about it and I learned more about epilepsy, we quickly realized that there are a substantial number of patients with epilepsy or seizure disorders where we cant do a genetic test to figure out what drug to use on those patients.

Clinical guidance, like Howards expertise, allows him to make a pretty good diagnosis and know what drugs to try first and second and third. But around 30 percent of children that come in with epilepsy never find the drug that works, and theyre in for a lifetime of trial-and-error. We realized that we could use iPSC-derived neurons to test drugs in the dish instead of going through all of the trial-and-error with patients. Thats the bigger project that weve been moving toward.

The Bow Foundation was formed by patient advocates after this rare genetic mutation in GNAO1 was identified. GNAO1 is a subunit of a G protein-coupled receptor; some mutations in this receptor can lead to epilepsy while others lead to movement disorders.

Were still trying to learn about these patients, and the biggest thing the Bow Foundation is doing is trying to address that by creating a patient registry. At the same time, the foundation has provided funds for us to start making and testing iPSCs and launch this approach to personalized medicine for epilepsy.

In the GNAO1 patients, we expect to be able to study their neurons in a dish and understand why they behave differently, why the electrical activity in their brain is different or why they develop differently.

Q. What other more widespread disorders, in addition to schizophrenia and epilepsy, are likely to benefit from your research?

A. Im part of a broader project called the Brain Somatic Mosaicism Network that is conducting research on diseases that span the neuropsychiatric field. Our lab covers schizophrenia, but other nodes within that network are researching autism, bipolar disorder, Tourette syndrome and other psychiatric diseases where the genetic cause is difficult to identify. Thats the underlying theme.

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Researcher Seeks to Unravel the Brain's Genetic Tapestry to Tackle Rare Disorder - University of Virginia

Skin Stem Cells Comments Off on Researcher Seeks to Unravel the Brain’s Genetic Tapestry to Tackle Rare Disorder – University of Virginia | August 22nd, 2017

Deadly gene mutations removed from human embryos in landmark study, reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause an often-fatal heart condition called hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, its unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure that the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and HarryB. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in the peer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While their reports were mostly accurate, ITV News, Sky News and The Independent over-stated the current stage of research, with Sky News and ITV News saying it could eradicate thousands of inherited conditions and the Independent claiming it opens the possibility for inherited diseases to be wiped out entirely. While this may be possible, we dont know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to designer babies, which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) its simply not possible to use genetic editing to select desirable characteristics - most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series of experiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos. This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesnt tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days. They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all cells in an embryo, or just some of them.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as theres a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so cant be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of mosaic embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If that happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture. They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

Only 28% of the stem cells were affected by the CRISPR-cas9 technique. Of these, most repaired themselves by joining the ends together, and only 41% were repaired by using a corrected version of the gene.

67% of the embryos exposed to CRISPR-cas9 had only the correct version of the gene higher than the 50% that would have been expected had the technique not been used. 33% of embryos had the mutated version of the gene, either in some or all their cells.

Importantly, the embryos didnt seem to use the template injected into the zygote to carry out the repair, in the way the stem cells did. They used the female version of the healthy gene to carry out the repair, instead.

Of the embryos created using CRISPR-cas9 at the point of fertilisation, 72% had the correct version of the gene in all their cells, and 28% had the mutated version of the gene in all their cells. No embryos were mosaic a mixture of cells with different genomes.

The researchers found no evidence of mutations induced by the technique, when they examined the cells using a variety of techniques. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos employ a different DNA damage repair system to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that targeted gene correction could potentially rescue a substantial portion of mutant human embryos, and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that despite remarkable targeting efficiency, CRISPR-cas9-treated embryos would not currently be suitable for transfer. Genome editing approaches must be further optimised before clinical application can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it on to their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos. However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to designer babies, where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And its likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is "playing God" or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that its rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing fast. This research shows just how close we are getting to making genetic editing of human embryos a reality.

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Gene editing used to repair diseased genes in embryos - NHS Choices

Skin Stem Cells Comments Off on Gene editing used to repair diseased genes in embryos – NHS Choices | August 22nd, 2017

Vitamin C may prompt faulty stem cells in bone marrow to die off, rather than multiplying to spur blood cancers.

A new study has found that vitamin C may communicate to faulty stem cells within bone marrow that they should mature and perish in a normal manner rather than multiplying to spur blood cancers. This is the insight gleaned from a study spearheaded by NYU Langone Health Perlmutter Cancer Center researchers. Study details were recently published in Cell.

About the Findings

The authors of the study state specific genetic alterations are known to decrease the ability of an enzyme referred to as tet methylcytosine dioxygenase 2 (TET2) to promote stem cell maturation and death in patients who have specific types of leukemia. They determined vitamin C activates TET2 functionality in mice designed to lack the enzyme. It is possible that vitamin C will prove to be a safe and effective treatment for diseases spurred by leukemia stem cells deficient in TET2. It is likely that vitamin C will be used in combination with other targeted therapies.

Study Details

The researchers used genetically altered mice in which TET2 was turned off. These mice endured abnormal stem cell activity. Such changes were reversed when a genetic trick restored TET2 expression. Providing high doses of vitamin C functioned similarly to restoring TET2 functionality on a genetic level. Vitamin C's promotion of DNA demethylation caused stem cells to mature and limited the advancement of leukemia cancer stem cells from humans that were implanted in mice. Vitamin C treatment affected leukemic stem cells similar to damaged DNA. Vitamin C was used in combination with a PARP inhibitor to produce an enhanced effect on such stem cells, sending them from self-renewal to maturity and subsequent death.

TET2 and Cancer

Alterations in the genetic code that decrease TET2 functionality are found in 10% of those who have acute myeloid leukemia (AML). About one-third of patients with a form of preleukemia known as myelodysplastic syndrome and upwards of half of those with chronic myelomonocytic leukemia have such genetic code mutations. These cancers spur anemia, bleeding and infection risk as abnormal stem cells multiply within bone marrow until they block the production of blood cells. Recent tests show about 2.5% of cancer patients living in the United States might develop TET2 alterations. This includes some patients with solid tumors and lymphomas.

About Cell Death Switch

The results of the study center on the relationship between cytosine and TET2. Cytosine is one of the several letters of nucleic acidthat make up genes' DNA code. Each cell type has thesame genes yet each receives unique instructions to turn on only those required in a specific cellular context. Examples of such epigenetic mechanisms include DNA methylation. This is an attachment of a diminutive molecule to cytosine bases to put a halt to the action of a gene containing them. Gene expression within stem cells is fine-tuned when methyl groups are attached and removed. Stem cellexpressions can then mature and multiplyto form muscle, nerve, bone and other types of cells. The bone marrow holds stem cell pools as adulthood is reached until they can become replacement cells. Inpatients with leukemia, signals that typically tell blood stem cells to mature end up malfunctioning. This allows for endless multiplication and a self-renewing rather than the generation of regular white blood cells required to combat infection.

TET2 empowers an alteration in the molecular structure of methyl groups required for their removal from cytosines. Such demethylation activates genes that direct stem cells to mature and commence a countdown to self-destruction as a component of regular turnover. This functions as a means of combating cancer yet it is disrupted in blood cancer patients who have TET2 mutations.

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Vitamin C May Help Slay Blood Cancer Stem Cells - Anti Aging News

Bone Marrow Stem Cells Comments Off on Vitamin C May Help Slay Blood Cancer Stem Cells – Anti Aging News | August 22nd, 2017

The ABMDR team at the meeting with Archbishop Hovnan Derderian (center) and the Very Rev. Fr. Dajad Yardemian.

LOS ANGELESOn Sunday, August 20, during Holy Mass at St. Leon Cathedral in Burbank, Archbishop Hovnan Derderian, Primate of the Western Diocese, offered special prayers for patients of the Armenian Bone Marrow Donor Registry (ABMDR). In his sermon, the Archbishop praised the life-saving mission of ABMDR, and called on congregants to continue to support its work.

To raise public awareness of the ABMDR mission and encourage grassroots involvement in the organizations activities, the Western Diocese has observed a special Prayer Day in honor of ABMDR patients for the past several years. The Prayer Day is marked at St. Leon Cathedral as well as Armenian churches across Southern California.

In the course of his sermon on August 20, Archbishop Derderian stated that participating in the work of ABMDR is tantamount to praying and accomplishing a Godly mission. The Archbishop pledged the continuous support of the Diocese and appealed to all parishes to embrace the work of ABMDR, by joining its ranks as potential bone marrow stem cell donors, signing up as volunteers, and attending its public-benefit events such as the upcoming Match for Life, the ABMDRs 18th annual Gala, which will be held on Sunday, August 27, in Los Angeles.

The ABMDR team outside St. Leon Cathedral

Archbishop Derderian, who is one of ABMDRs most avid and longtime supporters, exemplifies the type of leadership that works tirelessly for the well-being of our community, said ABMDR president Dr. Frieda Jordan. We are honored and grateful for the Primates ongoing guidance and support.

Following the church service, numerous parishioners had the opportunity to become more familiar with the activities of ABMDR, as a team of Board members and volunteers from the organization answered questions and handed out information about becoming donors.

Subsequently Archbishop Derderian, along with the Very Rev. Fr. Dajad Yardemian, met with the ABMDR team at the Diocese. The discussion centered on ABMDRs most recent achievements as well as its plans for the immediate future. At the conclusion of the meeting, Archbishop Derderian presented scarves from Holy Echmiadzin to all members of the ABMDR team, as tokens of his appreciation.

Established in 1999, ABMDR, a nonprofit organization, helps Armenians and non-Armenians worldwide survive life-threatening blood-related illnesses by recruiting and matching donors to those requiring bone marrow stem cell transplants. To date, the registry has recruited over 29,000 donors in 42 countries across four continents, identified over 4,190 patients, and facilitated 30 bone marrow transplants. For more information, call (323) 663-3609 or visit abmdr.am.

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Archbishop Derderian Leads Prayers for ABMDR Patients at Diocese Churches - Asbarez Armenian News

Bone Marrow Stem Cells Comments Off on Archbishop Derderian Leads Prayers for ABMDR Patients at Diocese Churches – Asbarez Armenian News | August 22nd, 2017

Dr. Alexandre R. Colas is an assistant professor at SBP. Credit: James Short

Researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP), the Cardiovascular Institute at Stanford University and other institutions were surprised to discover that the four genes in the Id family play a crucial role in heart development, telling undifferentiated stem cells to form heart tubes and eventually muscle. While Id genes have long been known for their activity in neurons and blood cells, this is the first time they've been linked to heart development. These findings give scientists a new tool to create large numbers of cardiac cells to regenerate damaged heart tissue. The study was published in the journal Genes & Development.

"It has always been unclear what intra-cellular mechanism initiates cardiac cell fate from undifferentiated cells," says Alexandre Colas, Ph.D., assistant professor in the Development, Aging and Regeneration Program at SBP and corresponding author on the paper. "These genes are the earliest determinants of cardiac cell fate. This enables us to generate unlimited amounts of bona fide cardiac progenitors for regenerative purposes, disease modeling and drug discovery."

The international team, which included researchers from the International Centre for Genetic Engineering and Biotechnology in Italy, University Pierre and Marie Curie in France and the University of Coimbra in Portugal, combined CRISPR-Cas9 gene editing, high-throughput microRNA screening and other techniques to identify the role Id genes play in heart development.

In particular, CRISPR played a crucial role, allowing them to knock out all four Id genes. Previous studies had knocked out some of these genes, which led to damaged hearts. However, removing all four genes created mouse embryos with no hearts at all. This discovery comes after a decades-long effort to identify the genes responsible for heart development.

"This is a completely unanticipated pathway in making the heart," says co-author Mark Mercola, Ph.D., professor of Medicine at Stanford and adjunct professor at SBP. "People have been working for a hundred years to figure out how the heart is specified during development. Nobody in all that time had ever implicated the Id protein."

Further study showed Id genes enable heart formation by turning down the Tcf3 and Foxa2 proteins, which inhibit the process, and turning up Evx1, Grrp1 and Mesp1, which support the process.

In addition to contributing a new chapter in the understanding of heart development, this study illuminates a powerful technique to screen for protein function in complex phenotypical assays, which was previously co-developed by Colas and Mercola. This technology could have wide-spread impact throughout biology.

"On a technical level, this project succeeded because it combined high-throughput approaches with stem cells to functionally scan the entire proteome for individual proteins involved in making heart tissue," says Mercola. "It shows that we can effectively walk through the genome to find genes that control complex biology, like making heart cells or causing disease."

Understanding this pathway could ultimately jumpstart efforts to use stem cells to generate heart muscle and replace damaged tissue. In addition, because Id proteins are the earliest known mechanism to control cardiac cell fate, this work is an important milestone in understanding cardiovascular developmental biology.

"We've been influenced by the skeletal muscle development field, which found the regulator of myogenic lineage, or myoD," says Colas. "For decades, we have been trying to find the cardiac equivalent. The fact that Id genes are sufficient to direct stem cells to differentiate towards the cardiac lineage, and that you don't have a heart when you ablate them from the genome, suggests the Id family collectively is a candidate for cardioD."

Explore further: Discovery of a key regulatory gene in cardiac valve formation

More information: Thomas J. Cunningham et al, Id genes are essential for early heart formation, Genes & Development (2017). DOI: 10.1101/gad.300400.117

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Id genes play surprise role in cardiac development - Medical Xpress - Medical Xpress

Cardiac Stem Cells Comments Off on Id genes play surprise role in cardiac development – Medical Xpress – Medical Xpress | August 22nd, 2017

LOS ANGELES In the fight against cardiovascular disease, a new super-weapon is now even closer to deployment and its capabilities are turning out to be beyond expectations.

One of the most notorious killers facing humanity, cardiovascular disease, is responsible for about about 1 in every 3 deaths in the U.S., according to the American Heart Association. A new study aimed at combating the disease finds that stem cells, the controversial darlings of modern biomedical research, are not only showing promise in treating heart failure, but in rats are actually reversing problems associated with old age.

The way the cells work to reverse aging is fascinating, says Dr. Eduardo Marbn,one of the studys primary investigators, in a press release. They secrete tiny vesicles that are chock-full of signaling molecules such as RNA and proteins. The vesicles from young cells appear to contain all the needed instructions to turn back the clock.

Marbn, who serves as director of the Cedars-Sinai Heart Institute, explains this latest study builds on previous lab work and human trials which have shown promise in treating heart failure using cardiac stem cell infusions.

The specific type of stem cells used in the study are known as cardiosphere-derived cells or CDCs. The process to grow these cells was initially developed when Marbn was part of the Johns Hopkins University faculty.

While the latest research involving CDCs indicates possibilities that have previously been in the realm of science fiction, the scientists leading the charge urge restraint in face of the excitement.

This study didnt measure whether receiving the cardiosphere-derived cells extended lifespans, so we have a lot more work to do, says Dr. Lilian Grigorian-Shamagian, the studys first author. We have much to study, including whether CDCs need to come from a young donor to have the same rejuvenating effects and whether the extracellular vesicles are able to reproduce all the rejuvenating effects we detect with CDCs.

Nevertheless, the latest results of stem cell infusions in rats are startling. Not only did rats that received the CDCs experience improved heart function, they also had lengthened heart cell telomeres.

Telomeres, the protective caps at the ends of chromosomes, normally shrink with age. As telomere shrinkage is one of the most studied and least understood phenomenons associated with aging, the effect of CDCs on them is especially fascinating.

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Whats more, the researchers said the rats who received the treatment also had their exercise capacity increase by about 20 percent. They also regrew hair faster than rats that didnt receive the cells.

With these thrilling results only the latest in recent stem cell headlines, researchers caution the public that most treatments are still not ready for prime time.

Indeed, a recent Reuters article warned that stem cell therapy still is not approved to treat heart failure in the U.S., yet many unscrupulous clinics are offering questionable services anyway and charging tens of thousands of dollars for it. In some cases, researchers quoted in the article said these labs may not even be injecting stem cells, but rather a useless and dangerous mix of cellular debris.

The article also noted two patients died and another went blind after stem cell injection procedures in Florida clinics.

Still, the legitimate doctors and scientists working to push the frontier of medicine forward are very optimistic about the real possibilities of the therapy. The Cedars-Sinai team said they are also studying the use of stem cells in treating patients with Duchenne muscular dystrophy and patients with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients.

Their research on CDCs effects on aging was published this month in the European Heart Journal.

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Study: Cardiac Stem Cell Injections Reverse Effects of Aging - Study Finds

Cardiac Stem Cells Comments Off on Study: Cardiac Stem Cell Injections Reverse Effects of Aging – Study Finds | August 22nd, 2017

Howard University Hospital's Dr. Ermias Aytenfisu seeks to clear up misconceptions about marrow donation in the minority community.

WASHINGTON, D.C. (August 21, 2017) Elsa Nega is an Ethiopian-Canadian mother of two young children. She loves her children and wants to watch them grow. However, Nega has a rare form of blood cancer, leukemia, and needs a bone marrow transplant to survive.

Black patients like Nega are the least likely to find their suitable blood marrow match, according to Be The Match which is hosting a Stem Cell/Bone Marrow registry event at the Howard University College of Medicine on Wednesday, Aug. 30 between 11 a.m. and 3 p.m. The exact location for the registry drive is the lobby outside of room 1008 in the Numa P. Adams building.

Negas story began in February when she walked into her local ER and was rushed to intensive care. By the next morning Nega was diagnosed with Acute Lymphoblastic Leukemia (ALL) and started on chemo immediately. Unlike 90 percent of patients who go into remission after the first round of chemo, she did not.

Now, after three rounds of chemo, a bone marrow transplant is her only hope of recovery. Negas siblings were not a match and she is reaching out to the Washington region because of its large population of people of Ethiopian descent.

There are a lot of myths associated with marrow donation, said Amanda Holk, community engagement representative with the Be The Match in Washington, D.C. There is so much fear surrounding the process but most donors are back to work the next day.

ErmiasM. Aytenfisu, M.D., stroke medical director at Howard University Hospital said the most common way to donate bone marrow is through a procedure called peripheral stem cell donation. No surgery is involved. Donors receive medication to increase peripheral stem cells before the donation. On the day of donation, blood is removed through a needle on one arm and passed through a machine that separates out the blood-forming cells. Uncommonly marrow donation involves surgical techniques that use a special needle to take out blood forming cells. During the procedure, the patient is anesthetized and feels no pain.

Joining the bone marrow registry at the Howard University College of Medicine event involves a simple as a cheek swab and an application. A persons chance of being a match at that point is only 1 in 500. But, for a patient like Elsa, you could be the only one. Elsa does not have a single match on the registry although there are 30 million people signed up.

For more information, contact Amanda Holk via email AHolk@nmdp.org or 202-875-9987

For the Howard University registry drive, please note that you must be between the ages of 18 and 44 to join the registry since research has shown that the younger the cells, the better the patient outcomes. And the following conditions prevent you from joining:

Hepatitis B or C

HIV

Organ, marrow or stem cell transplant recipient

Stroke or TIA (transient ischemic attack)

Other upcoming local events to support Elsa Nega:

*Empower the community (The Helen Show)

Date: 08/26/2017 (Sat.)

Location: Washington Convention Center

*Ethiopian Day Festival

Date: 09/03/2017 (Sun.)

Location: Downtown Silver Spring

About Howard University Hospital

Over the course of its roughly 155-year history of providing the finest primary, secondary and tertiary health care services, Howard University Hospital (HUH) remains one of the most comprehensive health care facilities in the Washington, D.C. metropolitan area and designated a DC Level 1 Trauma Center. The hospital is the nation's only teaching hospital located on the campus of a historically Black university. For more information, visit huhealthcare.com

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Howard University Hosts 'Be The Match' Marrow Registry Drive - Howard Newsroom (press release)

Bone Marrow Stem Cells Comments Off on Howard University Hosts ‘Be The Match’ Marrow Registry Drive – Howard Newsroom (press release) | August 22nd, 2017

VistaGen Therapeutics has received a notice of allowance for a stem cell production patent, which the firm says could be used in autoimmune disorder and cancer treatments.

The US Patent and Trademark Office (USPTO) issued VistaStem a subsidiary of VistaGen the notice for patent no. 14/359,517, which covers methods for producing hematopoietic precursor stem cells usually found in red blood marrow.

These are stem cells that give rise to all of the blood cells and most of the bone marrow cells in the body, with potential to impact both direct and supportive therapy for autoimmune disorders and cancer, said VistaGen VP Mark McPartland.

With CAR-T cell applications and foundational technology, McPartland said he believed the technology will provide approaches for producing bone marrow stem cells for bone marrow transfusions.

Business opportunities

In December last year, VistaGen signed an exclusive sublicense agreement with stem cell research firm BlueRock Therapeutics, under which the latter paid VistaGen $1.25m (1.06m) upfront for its cardiac stem cell production technologies.

McPartland said he expects this recent notice of allowance to also create potential opportunities for additional regenerative medicine transactions.

IP portfolio growth

VistaGen told us it plans to secure IP protection in multiple domains and international jurisdictions.

We intend to grow our IP portfolio in a manner that emphasises platform protection and maximises opportunities for commercialisation and out-licensing, McPartland said.

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VistaGen's cell production methods receive US patent boost - BioPharma-Reporter.com

Bone Marrow Stem Cells Comments Off on VistaGen’s cell production methods receive US patent boost – BioPharma-Reporter.com | August 22nd, 2017

There is truth in the old proverb about apple consumption and medical appointments. Insufficient vitamin C can contribute to leukemia. This observed relationship has now been shown to operate through the regulatory role the vitamin plays in the operation of bone marrow stem cells.

These days messages touting a single ingredient as being capable of curing all ills are more likely to peddleturmeric or cannabis, but a few decades ago it was vitamin C that was hailedas preventing everything from theflu to cancer if you took enough. As exaggerated as most of these claims were, it's certainly true that ascorbate, as it is also known, is vital to our health, sometimes in ways that are still unexplained.

We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we havent fully understood why, said Dr Sean Morrison of Childrens Medical Center Research Institute UT Southwestern. Stem cells clearly played a part, but are so rare in any individual tissue that it is impossible to collect the millions usually used for metabolic analysis. Moreover, most mammals make their own ascorbate, but humans cannot, impeding the use of animal models.

Morrison and his co-authors of a paper published in Nature had to develop new techniques to measure metabolite usage in populations as small as 10,000 stem cells to address the first problem. On applying these techniques the authors discovered each type of blood-forming cell has a distinctive signature to its metabolite consumption. They tackled the second problem using mice that lack ascorbate-producing enzymes.

When given a low vitamin C diet these mice had more, and more active, bone marrow stem cells, increasing blood cell production at the price of higher rates of leukemia. The vitamin C concentration was related to levels of the enzyme Tet2, which regulates blood production. Without enough Tet2, the stem cells behaved like an overheating engine, turning out blood cells at a great rate until they turned cancerous. Something similar is observed when mutations reduce Tet2 production.

The first clinical application of the discovery is for patients with clonal hematopoiesis, a condition that often involves reduced Tet2 production and leukemia. Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement, Morrison said. These patients... need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer.

Since stem cells are much sparser in the rest of the body than in bone marrow it will be even more challenging to extend the research to other cancers.

The ideal dose of vitamin C remains to be established, although a paper, coincidentally published last week, may indicate benefits beyond current recommendations.

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Vitamin C Can Suppress Leukemia Up To a Point | IFLScience - IFLScience

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Home Cancer The power of vitamin C: Can it kill cancer stem cells?

Every three minutes, one person in the United States is diagnosed with blood cancer. Thankfully, there may be a new approach to helping these individuals fight it using vitamin C.

Researchers from Perlmutter Cancer Center at NYU Langone Health recently published a report in the journal Cell indicating that vitamin C may be able to tell faulty cells in bone marrow to mature and die instead of multiplying to cause blood cancers. They explained that specific genetic changes are able to reduce the ability of the enzyme known as TET2 to push stem cells to mature, which die in many people who suffer from leukemia. Experts discovered that vitamin C seemed to activate TET2 in mice that were engineered to be TET2 deficient. In simple terms, TET2 is a tumor suppressor that can prevent certain cells from growing uncontrollably.

Mutations that reduce TET2 function are present in about 10 percent of people with acute myeloid leukemia, 30 percent of patients with a pre-leukemia known as myelodysplastic syndrome, and close to 50 percent of people with chronic myelomonocytic leukemia. Tests indicate that about 2.5 percent of U.S. cancer patients develop TET2 mutations, including some with lymphomas.

The study focused on the relationship between TET2 and cytosine, which is one of four nucleic acid letters that make up the DNA codes in our genes. The attachment of a small molecule, referred to as a methyl group, to cytosine bases can shut down the actions of a gene. As the human body forms, the attachment and removal of methyl groups adjust gene expression in stem cells, which can mature and become muscle, bone, nerve, or other cell types. The bone marrow keeps stem cells in pools, ready to become replacement cells when and if needed. In the case of leukemia, the signals that are supposed to tell a blood stem cell to mature end up malfunctioning, leaving it to multiply instead of developing normal white cells, which are needed to help fight infection.

Medical scientists explain that TET2 allows for a change in methyl groups that are required to be removed from cytosine. This essentially turns on genes and directs stem cells to mature and eventually destroy themselves. Researchers say that this signals an anti-cancer mechanism, something that can help blood cancer patients with TET2 mutations.

The team of researchers genetically engineered mice to manipulate the TET2 gene. Techniques to turn off TET2 in mice lead to abnormal stem cell behavior. The changes were reversed when TET2 was restored. Since previous work indicated that vitamin C could stimulate TET2, the researchers theorized that high doses of vitamin C might reverse the effects of TET2 deficiency. It would be a case of turning up the action on the functional gene. As it turns out, high dose vitamin C treatment did induce stem cells to mature and also suppressed the growth of leukemia cancer cells implanted in mice.

As of now, the NYU team is working on identifying genetic changes that may contribute to the risk of leukemia in specific groups of patients. While this latest study provides some hope for blood cancer patients, the manipulation of TET2 is only a potential new treatment approach until further studies are conducted. Currently approved treatments for blood cancers include stem cell transplantation, chemotherapy, and radiation therapy.

Related: Combining antibiotics and vitamin C helps to combat cancer stem cells

Related Reading:

Mangos show signs of reducing IBS symptoms and potential cancer risk

A simple blood test may soon detect cancer

http://www.cancercenter.com/terms/blood-cancers/https://ghr.nlm.nih.gov/gene/TET2

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The power of vitamin C: Can it kill cancer stem cells? - Bel Marra Health

Bone Marrow Stem Cells Comments Off on The power of vitamin C: Can it kill cancer stem cells? – Bel Marra Health | August 22nd, 2017

When Alex Shorheardthat he was a match for a stranger in Israel who would likely die without a stem cell transplant, he didn't think twice before saying "yes."

"If I today I help somebody, tomorrow I want somebody to help me too if I [am] sick," said Shor. "I don't think too much about it."

The request came from Ezer Mizion, an Israeli health service with the world's largest Jewish bone marrow registry, countingover 850,000 registrants worldwide. Shor said the representative told him the recipient would be a63-year-old man in Israel.

Shor, 41, had registered his DNA with the registry 10 years ago when he lived in Israel.

Shor and his family emigrated to Winnipeg nearly three years ago. In March, he got word that his stem cells were a match.

Stem cells are immature blood cells that can grow into healthy cells. They can make the difference between life and death for people with various forms of cancer, blood-related illnesses and metabolic disorders.

Shorwas agenetic match for the man based on the human leukocyte antigen (HLA) system, which codes the human immune system. The pair would have had to have 10 of the same HLA markers to be a viable match.

In May, Shorwent to a lab in Winnipeg to draw blood to send off to Israel to ensure hisblood would be compatible with the recipient's. Now, he plans to travel to Israel to donate his stem cells as soon as he hears from the physicians that the patient's condition has improved enough to tolerate the procedure.

Getting Shor's blood to Israel required a cooler, a courier and some creativity.

Vials of Shor's blood were transported to Israel in an ice-packed Thermos.

Dena Bensalmon, Canadian director of Israeli health service Ezer Mizion, put out a call on Facebook for a chaperone that could transport five vials of Shor's blood.

"Sixteen people came forward within about four minutes," she said.

One woman the perfect candidate was travelling from Winnipeg to Toronto, then on to Isreal. They packed the blood in ice in a Coleman thermos for the 12-hour journey.

"I met Dina in Toronto and then I switched the ice packs. They took the blood directly," she said.

Canada'sOneMatchregistry through Canadian Blood Serviceshas about 400,000 registrants.

But"if a person is Jewish, then the chances of them finding their match on a Jewish registry is far greater than them finding their match on a non-Jewish registry," saidBensalmon.

Canadian Blood Services has access to nearly 29 million volunteer donors and more than 720,000 cord blood units from dozens of countries around the world, as all the registries are connected under the umbrella of the World Marrow Donor Association, comprised of millions of people from across the world.

"I find the whole thing almost like watching a circle of life," said Bensalmon.

A volunteer brought vials of Shor's blood to Israel. She kept the thermos in her lap the whole 12-hour trip.

Shor said he just thought of his own father and how he would want someone to help him if he had a life-threatening illness. He encourages everyone to join a stem-cell registry.

"Tomorrow you may save somebody and tomorrow you don't know if you be sick and somebody save you," said Shor.

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Winnipeg man to donate stem cells to critically ill stranger in Israel - CBC.ca

Bone Marrow Stem Cells Comments Off on Winnipeg man to donate stem cells to critically ill stranger in Israel – CBC.ca | August 22nd, 2017

Madalayna Ducharme is celebrating her first birthday, on Aug, 22, 2017. She's shown recently in a family pool.Courtesy of the Ducharme family / Windsor Star

Bowling for Bone Marrow fundraiser Saturday

To support the families of those who need astem cell/bone marrow transplant, head to this weekends 12th annual Bowling for Bone Marrow Throw a Strike for the Gift of Life.

The Katelyn Bedard Bone Marrow Association fundraiser is Saturday at Rose Bowl Lanes with a noon check-in time and bowling between 1 and 3 p.m. Walk-ins are welcome and the cost is $20 without a pledge form.Children under age 12 get in free and there will be a clown and childrens activities.

To register, call (519) 564-4119 or go online atwww.givemarrow.net/index.html.

Windsors warrior princess Madalayna Ducharme celebrates her first birthday Tuesday.

Were so happy and grateful that weve had her for a year, her mom, Tamara Ducharme, said Monday. I know back at the six-month mark we had a little celebration for her just in case we didnt have a year birthday.

On March 17, little Madalayna received a bone marrow transplant to save her from a rare genetic disorder.

Madalayna will get to try cake for the first time, even if its just for her tiny fingers to play in, and her mom plans to go live on Facebook in the late afternoon for the approximately 3,000 supportive followers on the Miracle for Madalaynasite.

I cant believe how many people love her and support us. It makes us so happy, Ducharme said. We could be going through this alone. I feel like there are 3,000 fighters in our corner.

Madalayna, dubbed the warrior princess, was just two months old when doctors noticed issues that a few months later would be diagnosed as malignant infantile osteopetrosis which leads toabnormal thickening of the bone. Without treatment, the one-in-200,000 genetic disorder would dramatically reduce the infants life expectancy.

The Windsor community rallied around the family, and there were efforts made to get more people to join the bone marrow registry. Ducharme said shes thankful for the support from the Katelyn Bedard Bone Marrow Association. She said getting swabbed for the registry wasnt just for Madalayna but to help all those waiting for a match.

Because of the genetic disorder, at first doctors werent looking to family members for a match but Madalaynas two-year-old brother Henrik proved a perfect match and doctors consulted in the United States and Europe agreed his bone marrow was the familys best option.

The family didnt get Madalayna home from Toronto and London hospitals until July, and the little warrior fought off a virus that is worrisome with transplant patients, her mom said. So far, blood tests are looking good but the family wont know until after more extensive tests later this week in Toronto whether the transplant is working.

Ducharme is asking for prayers for good news in Toronto. The transplant is as close to a cure as possible, she said. Madalayna may have hearing and sight issues from the disease, but if the bones look better and the transplant is working, it gives her a chance at a longer life. Ducharme has heard of a man who had the disease and a transplant as a baby and is now 25 years old.

Madalyna, who loves music and looks like a princess in her tutu and frilly dresses, is a bit delayed with all that shes been through, but a week ago she sat up for the first time and she likes to dance by bouncing and swaying to techno music. She still needs the tube in her nose and doesnt like drinking liquids and isnt eating properly. Shes improving but her mom doesnt know what her baby will think of birthday cake.

Were excited.

shill@postmedia.com

twitter.com/winstarhill

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First birthday for Windsor's 'warrior princess' after lifesaving transplant - Windsor Star

Bone Marrow Stem Cells Comments Off on First birthday for Windsor’s ‘warrior princess’ after lifesaving transplant – Windsor Star | August 22nd, 2017

What if one day, we could teach our bodies to self-heal like a lizards tail, and make severe injury or disease no more threatening than a paper cut?

Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimers or Parkinsons disease?

Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.

ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institutes Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.

One of the things that that attracted me most to the ASU and the Biodesign CMDB was Haos vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology, Stephanopoulos said.

I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice.

Yans research center uses DNA and other basic building blocks to build their nanotechnology structures only at a scale 1,000 times smaller than the width of a human hair.

Theyve already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.

To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physics and the creative imaginations of these budding nano-architects.

Learning from nature

The goal of the Center for Molecular Design and Biomimetics is to usenatures design rulesas an inspiration in advancing biomedical, energy and electronics innovation throughself-assembling moleculesto create intelligent materials for better component control and for synthesis intohigher-order systems, said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.

Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeleys Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.

Weve learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems, Stephanopoulos said.

Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.

Stephanopoulos tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.

DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity, Stephanopoulos said.

Proof all in the design

During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.

Now, more recently, in a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.

In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.

To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.

By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to grab the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.

This new duplex can then be washed away, turning the signal off. To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the materials surface.

One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.

One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinsons disease.

The patients own skin cells could be converted to stem cells using existing techniques. The new technology could help expand the newly converted stem cells back in the lab and then direct their growth into specific dopamine-producing neurons before transplantation back to the patient.

People would love to have cell therapies that utilize stem cells derived from their own bodies to regenerate tissue, Stupp said. In principle, this will eventually be possible, but one needs procedures that are effective at expanding and differentiating cells in order to do so. Our technology does that.

In the future, it might be possible to perform this process entirely within the body. The stem cells would be implanted in the clinic, encapsulated in the type of material described in the new work, and injected into a particular spot. Then the soluble peptide-DNA molecules would be given to the patient to bind to the material and manipulate the proliferation and differentiation of transplanted cells.

Scaling the barriers

One of the future challenges in this area will be to develop materials that can respond better to external stimuli and reconfigure their physical or chemical properties accordingly.

Biological systems are complex, and treating injury or disease will in many cases necessitate a material that can mimic the complex spatiotemporal dynamics of the tissues they are used to treat, Stephanopoulos said.

It is likely that hybrid systems that combine multiple chemical elements will be necessary; some components may provide structure, others biological signaling and yet others a switchable element to imbue dynamic ability to the material.

A second challenge, and opportunity, for regenerative medicine lies in creating nanostructures that can organize material across multiple length scales. Biological systems themselves are hierarchically organized: from molecules to cells to tissues, and up to entire organisms.

Consider that for all of us, life starts simple, with just a single cell. By the time we reach adulthood, every adult human body is its own universe of cells, with recent estimates of 37 trillion or so. The human brain alone has 100 billion cells or about the same number of cells as stars in the Milky Way galaxy.

But over the course of a life, or by disease, whole constellations of cells are lost due to the ravages of time or the genetic blueprints going awry.

Collaborative DNA

To overcome these obstacles, much more research funding and recruitment of additional talent to ASU will be needed to build the necessary regenerative medicine workforce.

Last year, Stephanopoulos research received a boost with funding from the U.S. Air Forces Young Investigator Research Program (YIP).

The Air Force Office of Scientific ResearchYIP award will facilitate Nicks research agenda in this direction, and is a significant recognition of his creativity and track record at the early stage of his careers, Yan said.

Theyll need this and more to meet the ultimate challenge in the development of self-assembled biomaterials and translation to clinical applications.

Buoyed by the funding, during the next research steps, Stephanopoulos wants to further expand horizons with collaborations from other ASU colleagues to take his research teams efforts one step closer to the clinic.

ASU and the Biodesign Institute also offer world-class researchers in engineering, physics and biology for collaborations, not to mention close ties with the Mayo Clinic or a number of Phoenix-area institutes so we can translate our materials to medically relevant applications, Stephanopoulos said.

There is growing recognition that regenerative medicine in the Valley could be a win-win for the area, in delivering new cures to patients and building, person by person, a brand-new medicinal manufacturing industry.

Stephanopoulos recent research was carried out at Stupps Northwesterns Simpson Querrey Institute for BioNanotechnology. The National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant 5R01DE015920) provided funding for biological experiments, and the U.S. Department of Energy, Office of Science, Basic Energy Sciences provided funding for the development of the new materials (grants DE-FG01-00ER45810 and DE-SC0000989 supporting an Energy Frontiers Research Center on Bio-Inspired Energy Science (CBES)).

The paper is titled Instructing cells with programmable peptide DNA hybrids. Samuel I. Stupp is the senior author of the paper, and post-doctoral fellows Ronit Freeman and Nicholas Stephanopoulos are primary authors.

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Bio-inspired Materials Give Boost to Regenerative Medicine - Bioscience Technology

Spinal Cord Stem Cells Comments Off on Bio-inspired Materials Give Boost to Regenerative Medicine – Bioscience Technology | August 22nd, 2017

First came the prospect of pigs incubating human organs. Now a medical ethicist is raising new moral questions by suggesting scientists create human-animal chimeras to produce human eggs.

While the goal, for now, would be to create a ready supply of eggs purely for biomedical research purposes, should the hybrid human eggs turn out to be as good as ones produced by humans, I do not see any reason for not using them for treating human infertility, said Csar Palacios-Gonzlez, of the Centre of Medical Law and Ethics at Kings College London.

In a commentary in Reproductive BioMedicine Online, Palacios-Gonzlez tests arguments against creating chimeras for human gamete production, and finds all of them wanting.

Despite ongoing research and scientific and ethical discussions about the development of chimeras capable of producing solid organs such as kidneys and hearts for transplantation purposes, he writes, no wide discussion of the possibility of creating chimeras-IHGP (intended for human gamete production) has taken place. If anything, scientists have fallen over themselves to reassure the public steps will be taken to avoid creating such creatures.

A leading Canadian reproductive biologist called the paper deeply thought provoking and says the idea isnt outside the realm of possibility.

Humans are mammals and there is really nothing intrinsically different about the process of reproduction between humans and every other mammal, said Roger Pierson, a world expert on ovarian physiology at the University of Saskatchewan.

There is really nothing intrinsically different about the process of reproduction between humans and every other mammal

Were talking here not about what the combination of mammalian gametes might become, but were talking about the actual biological processes of passing our DNA from one generation to the next, he said.

The biology that comes out of this analysis is questioning some of the tenets of our assumptions about reproduction.

In theory, the process could involve interspecies blastocyst complementation the same technique researchers are exploring to create pigs capable of generating human organs for transplant.

A blastocyst an early embryo is taken from an animal and genes crucial for the development of a particular cell line or organ edited out. In this case you would aim at the reproductive system, Palacios-Gonzlez said in an interview.

Next, human pluripotent stem cells (cells that have the potential to develop into any type of tissue in the body) taken from a donors skin are injected into the blastocyst to compensate for the existing niche, he said. In this case human stem cells would complete the reproductive system, which would then create gametes.

What conceivably could result is the ovary of a sow (or cow or other animal) that produces human eggs.

In January, Salk Institute scientists reported in the journal Cell they had succeeded in creating the first human-pig chimera embryos. None were allowed to grow beyond four weeks and half were abnormally small. But in others, the human stem cells survived and turned into progenitors for different tissues and organs.

The achievement was hailed a scientific tour de force. It also rattled ethicists, who warned of the remote but not impossible risk human stem cells intended to morph into a new liver, pancreas or heart could wend their up to the animals brain, raising the prospect of a chimera with human consciousness.

Others worried about transplanted human stem cells generating reproductive tissues. Few people want to see what might result from the union between a pig with human sperm and a sow with human eggs, the New York Times warned.

Palacios-Gonzlez said that as far as he is aware, no one is actively pursuing creating chimeras capable of producing human sperm or eggs. But maybe I am wrong, the world is just too big. (The research that comes closest, he said, was published in 2014, when stem cells were taken from a skin sample from a man who produced no sperm and transplanted into the testicles of a mouse, where they became immature sperm.)

However, Palacios-Gonzlez argues that claims that the creation of chimeras violates human dignity are just false.

Most dont consider lab mice grafted with human cells such a violation, he writes in Reproductive BioMedicine.Neither do we consider that human dignity is violated when someone receives a pig heart valve, which effectivelyturnsthem into a chimera.

If human dignity is tied tothe possession of certain higher mental capacities, he added, gene-editing tools like CRISPR could be used to avoid generating brain tissue, thereby reducingthe possibility of accidentally creating a chimera with human brain cells.

Fears a human egg-producing chimera could become pregnant is a practical issue that could easily be avoided by, for example, creating only female chimeras, he writes.This would be the most sensible thing to do given that there is no shortage of human sperm for research purposes.

Even if it should one day become desirable to create chimeras capable of producing both eggs and sperm,we could just take the appropriate measures for (the chimeras) to be segregated by sex.

He also argues that whether generated by humans or chimeras human gametes do not possess intrinsic worth capable of being debased and that the eggs incubated by chimeras could go toward research capable of saving peoples lives.

Pierson said that, with focused work and funding, this kind of work could be done in probably a year or less. This is not far fetched.

This is not about having a male mouse thats ejaculating human sperm, coupled with a female mouse thats ovulating human eggs and creating a human embryo in the mouse, Pierson said.

Rather, among research questions, Its about understanding what our reproductive processes are and what they could become, he said. We need to lay down the ethical principles for exploring these new types of ideas.

Pierson said it could be the next step toward the completely lab-based generation of sperm and eggs. In vitro gametogenesis, or IVG, a technique still in its infancy, is aimed at creating functional sperm and eggs from induced stem cells. Last year, researchers in Japan reported in the journal Nature they had created mouse pups born from eggs created in a petri dish.

Pierson said any eggs generated from a nonperson chimera would likely come from a cow, and not a mouse, noting cows and humans share similar ovarian function.

NYU School of Medicine bioethicist Arthur Caplan said the technology is a decade or more away and would need safety testing in animals for another few years, if it even worked.

Safety issues are huge for chimeras, just huge, he added, including unknown mutations, subtle chemical differences in the derived eggs and the risk of communicating animal viruses.

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No moral reason not to create chimeras capable of making human eggs, ethicist argues - National Post

Skin Stem Cells Comments Off on No moral reason not to create chimeras capable of making human eggs, ethicist argues – National Post | August 22nd, 2017

How long do you expect to live?

Thats a question that can make a lot of people feel suddenly lost for an answer.

In fact, its not a question that anybody would like to answer.

However, for scientific, socio-economic, and other legitimate reasons, average life expectancy per region are being documented. According to the World Factbook by the Central Intelligence Agency, the average life expectancy at birth of the following countries as of 2016 are as follows:

The rest of the world has an average life expectancy of 80 years downwards, with Chad ranking the lowest at 50.20 years.

Life is short, too short.

Its the reason why the pursuit of anything and everything under the sun that can stop aging is mankinds obsession.

We want to live longer; if possible, forever.

Forever is definitely too, too far away. But, longer, yes. Its more probable.

Heres the latest news on anti-aging, and this time its about stem cells. Stem cells from a young heart may help in regaining vitality which we lose as we grow old.

Researchers from the Cedars-Sinai Heart Institute have recently discovered that upon application of Cardiosphere-derived cells (CDC), which they took from newborn mice and injected into the hearts of 22-month-old mice, had resulted to better heart functionality, hair regrowth at a faster rate, 20 percent longer exercise endurance, and longer cardiac telomeres.

The findings on the effect of CDC cells on telomeres is very significant since these compound structures located at the tip of chromosomes function as the cells time-keepers. In fact, another study is focusing on methods to lengthen telomeres to fight the effects of progeria and help prolong life.

Our previous lab studies and human clinical trials have shown promise in treating heart failure usingcardiac stem cell infusions, saidCedars-Sinai Heart Institute and lead researcher Eduardo Marbn, MD, PhD, Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.

According to Dr. Marban, the CDC cells work on reversing the aging process by secreting very small vesicles that are full of signaling molecules like proteins and ribonucleic acid (RNA). The vesicles appear to have all the necessary information in producing cardiac and systemic rejuvenation.

In 2009, the LA-based team achieved the worlds first stem cell infusion which they hope to use in treating patients with Duchenne muscular dystrophy and cases of heart failure with preserved ejection fraction. However, this was the first time that they have observed this kind of rejuvenating effects of CDC cells.

Nevertheless, Dr. Marban and his team acknowledge that they still have a lot to do and figure out. They havent determined yet if the CDC cells could lengthen life, or just produce a younger heart in an aged physique. They also have to find out if the cells must come from younger hearts for the stem cell treatment to be effective.They will obviously need more time and tests to find the right answers to these very important questions.

But, if Dr. Marban and his team succeed, CDC cells may be a key to restoring youth and vigor. It will also help globally the large number of people who suffer from cardiovascular diseases-heart disease is the worlds number 1 killer and accounts for 17.3 million deaths per year.

The study was published on theEuropean Heart Journal.

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In World First, Scientists Reverse Aging in Old Hearts by Injecting Younger Cells - Wall Street Pit

Cardiac Stem Cells Comments Off on In World First, Scientists Reverse Aging in Old Hearts by Injecting Younger Cells – Wall Street Pit | August 20th, 2017

Researchers at the Mayo Clinic and the University of Minnesota say theyre on the brink of a new era in cancer care one in which doctors extract a patients white blood cells, have them genetically engineered in a lab, and put them back to become personalized cancer-fighting machines.

The so-called CAR T cellular therapies are expected to receive federal approval this fall for certain rare blood cancers B-cell forms of lymphoma and leukemia. But scientists at the Minnesota institutions hope thats just the first step that will lead to better treatment of solid tumor cancers as well.

This is really the first approval of a genetically modified product for cancer therapy, said Dr. Jeffrey Miller, deputy director of the Masonic Cancer Center at the University of Minnesota. If the proof of concept works, he said, we might be on the right track to get away from all of that toxic chemotherapy that people hate.

Participating in industry-funded clinical trials, the Minnesota researchers hoped to determine if patients with leukemia or lymphoma would be more likely to survive if their own stem cells were extracted to grow cancer-fighting T-cells that were then infused back into their bodies.

One analysis, involving trials by Kite Pharmaceuticals at Mayo and other institutions, found a sevenfold increase in lymphoma patients whose cancers disappeared when they received CAR T instead of traditional chemo-based treatment.

I often tell patients that T-cells are like super robocops, said Dr. Yi Lin, a Mayo hematologist in Rochester. Were now directing those cells to really target cancer.

The U.S. Food and Drug Administration is widely expected this fall to approve CAR T products made by Kite and Novartis, which genetically engineer T-cells to target so-called CD19 proteins found on the surface of leukemia and lymphoma cells.

The side effects can be harsh, because the T-cell infusions trigger an immune system response that can produce fever, weakness, racing heart and kidney problems. Short-term memory and cognitive problems also have occurred. Brain swelling led to five deaths of cancer patients who took part in a CAR T trial by Juno Pharmaceuticals. The trial was shut down as a result.

Lin said brain swelling appeared mostly in adults with leukemia. For now, she expects Kites CAR T therapy to be approved for diffuse large B-cell lymphoma and the Novartis therapy to be approved for acute lymphoblastic leukemia in children. Federal regulations also might restrict CAR T for patients whose cancers survived traditional treatments.

Current practice to treat these cancers generally involves chemotherapy and radiation. Physicians then transplant stem cells, often from donor bone marrow, to regrow the patients immune systems, which are weakened in the process of treatment.

CAR T differs in that patients will receive infusions of their own T-cells, genetically modified, which their bodies will be less likely to reject.

Its individualized medicine, Lin said.

Im on my way

Before he tried CAR T at Mayo as part of a clinical trial, John Renze of Carroll, Iowa, had received two rounds of chemo, two rounds of radiation, and an experimental drug that did nothing to stop the spread of lymphoma.

After you fail about four times, you start to wonder if anything is going to work, the 58-year-old said.

At first, there was no room for him in the Mayo trial which has been a problem nationwide as desperate cancer patients have searched for treatment alternatives. But then he got the call one morning last summer while ordering coffee at his local cafe.

Can you get up here by one? the Mayo official asked.

Im on my way, Renze replied.

Even before federal approval comes through, researchers such as Miller are looking beyond the first-line CAR T therapies, and wondering if the approach can be used on solid tumors. Roughly 80,000 blood cancers occur each year in the U.S. that could be treated with CAR T, but the total number of cancers diagnosed each year is nearly 1.7 million.

The challenge is that solid tumors dont have the same protein targets as blood cancers. And T-cells would have to be more discriminating if infused to eliminate tumors in solid organs, Miller said. If you destroy normal lung tissue (along with lung cancer), thats not going to work, he said.

Mayo researchers are studying whether CAR T can work against multiple myeloma, a cancer of the bone marrow, while U researchers are exploring ways to better control the CAR T-cells after they are infused in cancer patients.

Researchers also are trying to understand whether CAR T produces memory in the immune system, so it knows to react if cancers resurface.

In addition, Miller is studying whether NK cells, which also play a role in the human immune system, can be genetically modified and infused instead of T-cells to target cancer. The body doesnt reject NK cells from donors as much, he said. So NK cells from donor bone marrow or umbilical cord blood could be collected and mass produced to potentially provide faster and cheaper treatments.

Like many breakthrough therapies, CAR T will be expensive, with a price likely to exceed $200,000 per patient. How insurers plan to cover it remains unclear. Blue Cross and Blue Shield of Minnesota is evaluating evidence regarding CAR Ts effectiveness, and will set a coverage policy after it receives FDA approval, said Dr. Glenn Pomerantz, Blue Cross chief medical officer.

A surge for Mayo?

Mayo expects a surge of hundreds of cancer patients per year if CAR T is approved, because it will initially be provided by large medical centers that have experience with the therapy and its side effects. The Rochester hospital is planning to add staff and space dedicated to CAR T.

Miller said the U is developing advice for referring doctors and hospitals statewide, so they know what to do if CAR T patients show up with complex symptoms.

They can be a bit delayed and you cant just keep people in the hospital to see if they develop these things, he said.

Renzes stem cells were taken last July, and his modified T-cells were put back a month later. He lost weight and felt sick for weeks, and had to drive three hours to Mayo for frequent checkups.

But as of last Aug. 31, the cancer had vanished.

Every three months, he returns to Mayo to make sure the cancer hasnt re-emerged. Then he returns to Carroll, where he owns farmland and car dealerships and dotes on his grandchildren.

For people like me that have already failed a bunch of times, youre happy to try anything, he said. I mean, what else would I have done?

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Mayo, U develop 'robocop' stem cells to fight cancer - StarTribune.com - Minneapolis Star Tribune

Bone Marrow Stem Cells Comments Off on Mayo, U develop ‘robocop’ stem cells to fight cancer – StarTribune.com – Minneapolis Star Tribune | August 20th, 2017

Representational image

Washington D.C. : A study has recently revealed that vitamin C may tell faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers.

According to researchers, certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia.

The new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

Corresponding study author Benjamin G. Neel said, "We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies."

The results suggested that changes in the genetic code (mutations) that reduce TET2 function are found in 10 percent of patients with acute myeloid leukemia (AML), 30 percent of those with a form of pre-leukemia called myelodysplastic syndrome, and in nearly 50 percent of patients with chronic myelomonocytic leukemia.

The study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid "letters" that comprise the DNA code in genes.

To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the team genetically engineered mice such that the scientists could switch the TET2 gene on or off.

The findings indicated that vitamin C did the same thing as restoring TET2 function genetically. By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukemia cancer stem cells from human patients implanted in mice.

"Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA," said first study author Luisa Cimmino.

"For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer," Cimmino added.

The findings appear in journal Cell.

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Vitamin C may help genes to kill blood cancer stem cells - ETHealthworld.com

Bone Marrow Stem Cells Comments Off on Vitamin C may help genes to kill blood cancer stem cells – ETHealthworld.com | August 20th, 2017

Yaron Ramati, Director of Regulatory Affairs at Pluristem Therapeutics

Over the past few years, the regulatory landscape for cell therapy development has grown increasingly complex. There are now accelerated pathways for advanced therapy medicinal products (ATMPs) in several countries worldwide, including the U.S., Japan, and South Korea. While the possibility for accelerated commercialization has resulted from these changes, substantial complexity has also been introduced, making it a more elaborate process to move cell therapy products from bench to bedside.

In the interview with Yaron Ramati, Director of Regulatory Affairs at Pluristem Therapeutics, we get an experts perspective on how the regulatory environment has changed and new opportunities that exist for bringing cell therapy products through the clinical trial process and into the global marketplace.

Yaron Ramati: I have 10 years of experience in regulatory affairs in biotechnology companies in Israel.

I have a PhD in Philosophy of Biology from the London School of Economics and an M.Sc. from the Technion in Neurobiology

Yaron Ramati:The United States, Japan, and South Korea are countries that have accelerated pathways that are unique for cell and gene therapies. Legislation took effect in Japan in late 2014, in South Korea in 2016, and in the United States in 2017.

Additionally, the EU has a program for product acceleration the Adaptive Pathways. Although it is not explicitly for cell and gene therapies, these have been given a lot of attention by the group.

Yaron Ramati:

In the United States: Regenerative medicine advanced therapy (RMAT) designation.Cell therapies that aim to treat serious medical conditions with high unmet need, and have preliminary favorable clinical data, can get the designation. It allows for accelerated approval (i.e., the use of biomarkers and intermediate endpoints for BLA, priority review).

In Japan: Conditional time-limited marketing authorization.This program allows for regenerative therapies (cell, gene and tissue therapies) to receive conditional marketing authorization for up to 7 years, following confirmation of safety and an initial proof of efficacy in Japan in diseases that are serious and have a high unmet need.

In South Korea: Conditional marketing authorization for cell therapy.As in Japan, this program allows for cell therapies to receive conditional marketing authorization for a limited time, following an initial proof of efficacy in serious diseases.

In EU: Adaptive Pathways pilot program. This program is a pilot program established by the EMA to explore ways in which the EMA can assist the streamlining the development of new promising therapies for serious conditions with high unmet need. Although this program is not explicitly for cell or gene therapy, it is the main focus of the group.

Yaron Ramati: All EU countries have a joint definition for ATMPs as set by EU regulation. Other countries have separate definitions that only partially overlap.

Yaron Ramati: Only few countries in the world are willing to be the first to provide marketing authorization for novel therapies. For ATMPs, European regulation does not allow individual countries in the union to provide marketing authorization, and so the EMA is the only gateway for ATMPs in Europe.

The U.S. FDA, Japan PMDA, and South Korea KFDA are the only others that are willing to be first to approve ATMPs.

Yaron Ramati: Currently, the EMA and PMDA are leading with four marketing approvals of cell and gene therapies each. RMAT designation procedure in the U.S. is expecting to give a boost to the products that are being developed for the U.S. market.

Yaron Ramati: Pluristem is very active in the field of accelerated development of its products. PLX-PAD of Pluristem has been accepted to the Japan conditional time-limited marketing authorization scheme by PMD, as well as to the adaptive pathways program of the EMA. It is active in both programs.

In addition, Pluristem intends to make use of the accelerated pathways offered for regenerative therapies in both the U.S. and in South Korea.

Yaron Ramati: The focus of Pluristem in these programs is the advancement of PLX-PAD. Pluristem had achieved understandings with EMA and PMDA regarding the accelerated approval of PLX-PAD for the treatment of critical limb ischemia (CLI).

It is the intention of Pluristem to achieve similar understandings with FDA, EMA, PMDA and KFDA regarding the development of PLX-PAD for the treatment of patients following hip fractures.

Yaron Ramati: PLX-PAD was accepted into the EMA adaptive pathways pilot program in 2015. Since then, Pluristem has taken advantage of this program in coming to an understanding with the EMA on the desired regulatory path of PLX-PAD in CLI. In addition, Pluristem undertook parallel scientific advice with the EMA and leading health technology assessment (HTA) bodies in Europe.

In this meeting, Pluristem received valuable feedback on the expectations that these bodies have for purposes of reimbursement in Europe. Pluristem has designed the Phase 3 PACE study in CLI patients in view of the feedback received from both the EMA and the HTA bodies, with the purpose of addressing their respective expectations.

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An Experts Perspective on Accelerated Pathways for Cell ...

IPS Cell Therapy Comments Off on An Experts Perspective on Accelerated Pathways for Cell … | August 20th, 2017

Those suffering from hair loss problems could soon be worry free thanks to a bunch of researchers at UCLA. The team found that by activating the stem cells in the hair follicles they could make it grow. This type of research couldnt come soon enough for some. We may have finally found a cure for patients suffering from alopecia or baldness.

Hair loss is often caused by the hair follicle stem cells inability to activate and induce a new hair growth cycle. In doing the study, researchers Heather Christofk and William Lowry, of Eli Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCLA discovered that the metabolism of hair follicle stem cells is far different to any other cell found within the skin. They found that as hair follicle stem cells absorb the glucose from the bloodstream they use it to produce a metabolite called pyruvate. The pyruvate is then either sent to the cells mitochondria to be converted back into energy or is converted into another metabolite called lactate.

Christofk is an associate professor of biological chemistry and molecular and medical pharmacology and he says, Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate and if that would activate the cells and grow hair more quickly. First, the team demonstrated how blocking the lactate production in mice prevented the hair follicle stem cells from activating. Then, with the help of colleagues at the Rutter lab at the University of Utah, they increased the lactate production in the mice and as a result saw an accelerated hair follicle stem cell activation and therefore an increase in the hair cycle.

Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect, confirms Lowry, a professor of molecular, cell and developmental biology. During the study, the team found two drugs in particular that influenced hair follicle stem cells to promote lactate production when applied to the skin of mice. The first is called RCGD423. This drug is responsible for allowing the transmission of information from outside the cell right to the heart of it in the nucleus by activating the cellular signaling pathway called JAK-Stat. The results from the study did, in fact, prove that JAK-Stat activation will lead to an increased production of lactate which will enhance hair growth. UK5099 was the second drug in question, and its role was to block the pyruvate from entering the mitochondria, forcing the production of lactate and accelerating hair growth as a result.

The study brings with it some very promising results. To be able to solve a problem that affects millions of people worldwide by using drugs to stimulate hair growth is brilliant. At the moment there is a provisional patent application thats been filed in respect of using RCGD423 in the promotion of hair growth and a separate provisional patent in place for the use of UK5099 for the same purpose. The drugs have not yet been tested in humans or approved by the Food and Drug Administration as fit for human consumption.

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Scientists Discover New Hair Growth Technique Using Stem Cells ... - TrendinTech

Skin Stem Cells Comments Off on Scientists Discover New Hair Growth Technique Using Stem Cells … – TrendinTech | August 19th, 2017