June 25, 2014 - Stem Cell Therapy / David Steenblock

By: Dennis Courtney

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June 25, 2014 - Stem Cell Therapy / David Steenblock - Video

Animal Cell Therapies - Tucker #39;s Story
Tucker shows notable improvement in gait and movement after receiving stem cell therapy from Animal Cell Therapies.

By: Animal Cell Therapies, Inc.

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Animal Cell Therapies - Tucker's Story - Video

By Jim Kasuba The News-Herald Twitter: @JKasuba

Elizabeth Disney (left) turned out to be a suitable blood stem donor for her sister, Brittany, who is afflicted with Burkitt lymphoma, considered to be an extremely rare disease for a young woman of only 23. Photo courtesy of Donna Smith

RIVERVIEW Battling a rare cancer has been a rough road for Brittany Disney, but the worst may be behind her.

The good news is that a suitable stem cell donor has been found and the transplant surgery went well. The not-so-good news is that theres a long recovery period and shes still in a lot of pain.

Donna Smith, a close friend of the family, said the young woman underwent stem cell replacement on June 6.

There was a one in four chance that a sibling would be a match, Smith said. (Her sister) Elizabeth had five out of six markers to be a stem cell donor for her.

Disney, 23, was diagnosed late last year with stage four Burkitt lymphoma, a form of non-Hodgkins lymphoma in which cancer starts in immune cells called B-cells. Recognized as the fastest growing human tumor, Burkitt lymphoma is associated with impaired immunity and is rapidly fatal if left untreated.

Burkitt lymphoma is so rare in young adult women that the Henry Ford Health System wrote about the case in a medical journal, said one of Disneys college friends.

In November, friends and family sponsored a spaghetti dinner fundraiser to assist the family with medical bills and expenses, but things continued to look bleak, as a stem cell transplant appeared to be the only answer to treating the condition.

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Riverview woman recovers from stem cell transplant; family seeking notes of encouragement

By LAURAN NEERGAARD AP Medical Writer

WASHINGTON (AP) - Bone marrow transplants save thousands of lives but patients are vulnerable to severe viral infections in the months afterward, until their new immune system kicks in. Now scientists are developing protection for that risky period - injections of cells specially designed to fend off up to five different viruses at once.

"These viruses are a huge problem, and there's a huge need for these products," said Dr. Ann Leen, who leads a team at Baylor College of Medicine and Texas Children's Hospital that found an easier way to produce these long-desired designer T cells.

Healthy people have an army of T cells that roams the body, primed to recognize and fight viruses. People with suppressed immune systems - such as those undergoing a bone marrow transplant to treat leukemia or other diseases - lack that protection. It can take anywhere from four months to more than a year for marrow stem cells from a healthy donor to take root and start producing new immune cells for the recipient. When patients get sick before then, today's antiviral medications don't always work and cause lots of side effects.

The proposed solution: Take certain virus-fighting T cells from that same bone marrow donor, and freeze them to use if the recipient gets sick. Years of experiments show it can work. But turning the idea into an easy-to-use treatment has been difficult. A dose had to be customized to each donor-recipient pair and protected against only one or two viruses. And it took as long as three months to make.

Wednesday, Leen reported a novel technique to rapidly manufacture so-called virus-specific T cells that can target up to five of the viruses that cause the most trouble for transplant patients: Epstein-Barr virus, adenovirus, cytomegalovirus, BK virus, and human herpesvirus 6.

Essentially, Leen came up with a recipe to stimulate donated T cells in the laboratory so that they better recognize those particular viruses, and then grow large quantities of the cells. It took just 10 days to create and freeze the designer T cells.

To see if they worked, Leen's team treated 11 transplant recipients. Eight had active infections, most with multiple viruses. The cell therapy proved more than 90 percent effective, nearly eliminating all the viruses from the blood of all the patients, Leen reported in the journal Science Translational Medicine.

The other three patients weren't sick but were deemed at high risk. They were given early doses of the T cells protectively and remained infection-free, Leen said.

Next, her team is beginning a bigger step - to try creating a bank of those cells from a variety of healthy donors that any patient could use, without having to custom-brew each dose.

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Designer T cells fight viruses after transplants - Quincy Herald-Whig | Illinois & Missouri News, Sports

PUBLIC RELEASE DATE:

24-Jun-2014

Contact: Jacob M. van Laar j.m.vanlaar@umcutrecht.nl The JAMA Network Journals

Among patients with a severe, life-threatening type of sclerosis, treatment with hematopoietic stem cell transplantation (HSCT), compared to intravenous infusion of the chemotherapeutic drug cyclophosphamide, was associated with an increased treatment-related risk of death in the first year, but better long-term survival, according to a study in the June 25 issue of JAMA.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy (a disorder of the blood vessels), low-grade inflammation, and fibrosis (development of excess fibrous connective tissue) in skin and internal organs. Previously, small studies have shown that systemic sclerosis is responsive to treatment with autologous HSCT, although it has been unclear whether HSCT improves survival, according to background information in the article. For this study, autologous HSCT involved a multistep process beginning with infusion of high doses of cyclophosphamide and an antibody against immune cells, followed by reinfusion of the patient's own stem cells that had been previously collected from blood and purified.

Jacob M. van Laar, M.D., Ph.D., of the University Medical Center Utrecht, Utrecht, the Netherlands and Dominique Farge M.D., Ph.D, of the Assistance Publique - Hopitaux de Paris, Paris 7 Diderot University, France, and colleagues randomly assigned 156 patients with early diffuse cutaneous (widespread skin involvement) systemic sclerosis to receive HSCT (n = 79) or cyclophosphamide (n = 77; 12 monthly infusions). The phase 3 clinical trial was conducted in 10 countries at 29 centers; patients were recruited from March 2001 to October 2009 and followed up until October 2013.

During a median follow-up of 5.8 years, 53 adverse events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). Patients treated with HSCT experienced more adverse events (including death) in the first year but had better long-term event-free survival than those treated with cyclophosphamide.

Patients in the HCST group experienced higher mortality in the first year but had better long-term overall survival than those treated with cyclophosphamide. During year 1 there were 11 deaths (13.9 percent, including 8 treatment-related deaths) in the HSCT group vs 7 (9.1 percent, no treatment-related deaths) in the control group. After year 2 of follow-up, there were 12 deaths (15.2 percent) in the HSCT group vs 13 (16.9 percent) in the control group. After 4 years of follow-up, there were 13 deaths (16.5 percent) in the HSCT group vs 20 (26.0 percent) in the control group.

The authors add that HSCT was also more effective than intravenous cyclophosphamide on measures evaluating skin, functional ability, quality of life, and lung function, consistent with previous studies.

"Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit," the authors conclude.

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Stem cell transplantation for severe sclerosis associated with improved long-term survival

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Newswise Among patients with a severe, life-threatening type of sclerosis, treatment with hematopoietic stem cell transplantation (HSCT), compared to intravenous infusion of the chemotherapeutic drug cyclophosphamide, was associated with an increased treatment-related risk of death in the first year, but better long-term survival, according to a study in the June 25 issue of JAMA.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy (a disorder of the blood vessels), low-grade inflammation, and fibrosis (development of excess fibrous connective tissue) in skin and internal organs. Previously, small studies have shown that systemic sclerosis is responsive to treatment with autologous HSCT, although it has been unclear whether HSCT improves survival, according to background information in the article. For this study, autologous HSCT involved a multistep process beginning with infusion of high doses of cyclophosphamide and an antibody against immune cells, followed by reinfusion of the patient's own stem cells that had been previously collected from blood and purified.

Jacob M. van Laar, M.D., Ph.D., of the University Medical Center Utrecht, Utrecht, the Netherlands and Dominique Farge M.D., Ph.D, of the Assistance Publique - Hopitaux de Paris, Paris 7 Diderot University, France, and colleagues randomly assigned 156 patients with early diffuse cutaneous (widespread skin involvement) systemic sclerosis to receive HSCT (n = 79) or cyclophosphamide (n = 77; 12 monthly infusions). The phase 3 clinical trial was conducted in 10 countries at 29 centers; patients were recruited from March 2001 to October 2009 and followed up until October 2013.

During a median follow-up of 5.8 years, 53 adverse events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). Patients treated with HSCT experienced more adverse events (including death) in the first year but had better long-term event-free survival than those treated with cyclophosphamide.

Patients in the HCST group experienced higher mortality in the first year but had better long-term overall survival than those treated with cyclophosphamide. During year 1 there were 11 deaths (13.9 percent, including 8 treatment-related deaths) in the HSCT group vs 7 (9.1 percent, no treatment-related deaths) in the control group. After year 2 of follow-up, there were 12 deaths (15.2 percent) in the HSCT group vs 13 (16.9 percent) in the control group. After 4 years of follow-up, there were 13 deaths (16.5 percent) in the HSCT group vs 20 (26.0 percent) in the control group.

The authors add that HSCT was also more effective than intravenous cyclophosphamide on measures evaluating skin, functional ability, quality of life, and lung function, consistent with previous studies.

Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit, the authors conclude. (doi:10.1001/jama.2014.6368; Available pre-embargo to the media at http://media.jamanetwork.com)

Editors Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Stem Cell Transplantation For Severe Sclerosis Linked With Improved Long-term Survival

EXTON, Pa.--(BUSINESS WIRE)--Fibrocell Science, Inc., (NYSE MKT:FCSC), an autologous cell therapy company primarily focused on developing first-in-class treatments for rare and serious skin and connective tissue diseases with high unmet medical needs, announced today that it has entered into an exclusive license agreement with The Regents of the University of California. Under the agreement, Fibrocell acquired the rights to commercially apply patented discoveries and technologies resulting from the ongoing scientific collaboration between the University of California at Los Angeles (UCLA) and Fibrocell Science.

The technologies from the UCLA collaboration and exclusive license agreements enable Fibrocell to expand its proprietary Personalized Biologics platform which uses human fibroblasts and stem cells from skin to create localized therapies that are compatible with the unique biology of each patient. Specifically, the newly licensed patents and technologies relate to two advancements in the therapeutic application of cell therapies:

The technologies from these licenses further strengthen Fibrocells rich development platform, said David Pernock, chairman and chief executive officer of Fibrocell. These potentially transformational technologies offer partnering opportunities for Fibrocell.

The license agreements build upon an existing research collaboration between Fibrocell and UCLA that has already yielded discoveries and technologies related to stem cells and regenerative cells in human skin. Such research is led by James A. Byrne, Ph.D., an Assistant Professor in UCLAs Department of Molecular and Medical Pharmacology at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

About Fibrocell Science, Inc.

Fibrocell Science, Inc. (NYSE MKT:FCSC) is an autologous cell therapy company primarily focused on developing first-in-class treatments for rare and serious skin and connective tissue diseases with high unmet medical needs. Based on its proprietary autologous fibroblast technology, Fibrocell is pursuing breakthrough medical applications of azficel-T for restrictive burn scarring and vocal cord scarring. The companys collaboration with Intrexon Corporation (NYSE:XON), a leader in synthetic biology, includes using genetically-modified fibroblasts for treating rare and serious skin and connective tissue diseases for which there are no currently approved products. For additional information, visit http://www.fibrocellscience.com.

About UCLA

UCLAis Californias largest university, with an enrollment of more than 40,000 undergraduate and graduate students. The UCLA College of Letters and Science and the universitys 11 professional schools feature renowned faculty and offer 337 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Seven alumni and six faculty have been awarded the Nobel Prize.

Forward-Looking Statements

This press release contains, and our officers and representatives may from time to time make, statements that are forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements include, among others, statements we make regarding (i) our ability to develop breakthrough therapies for the treatment of skin and connective tissues diseases and (ii) our ability to successfully leverage our relationship with UCLA to expand our proprietary Personalized Biologics platform. These forward-looking statements rely on a number of assumptions concerning future events and are subject to a number of risks, uncertainties, and other factors, many of which are outside of Fibrocell Sciences control. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: (i) uncertainties relating to the initiation and completion of clinical trials; (ii) whether clinical trial results will validate and support the safety and efficacy of azficel-T; and (iii) our ability to establish additional strategic partnerships, as well as those set forth under the caption Item 1A. Risk Factors in Fibrocell Sciences most recent Form 10-K filing, as updated in Item 1A. Risk Factors in Fibrocell Sciences most recent Form 10-Q filing. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. In addition, Fibrocell Science operates in a highly competitive and rapidly changing environment, and new risks may arise. Accordingly, you should not place any reliance on forward-looking statements as a prediction of actual results. Fibrocell Science disclaims any intention to, and undertakes no obligation to, update or revise any forward-looking statement. You are also urged to carefully review and consider the various disclosures in Fibrocell Sciences most recent annual report on Form 10-K, our most recent Form 10-Q as well as other public filings with the SEC since the filing of Fibrocell Sciences most recent annual report.

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FIbrocell Science Announces Exclusive Technology License Agreements with UCLA to Advance the Development of ...

stem cell therapy Egypt
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Dallas, TX (PRWEB) June 24, 2014

The birth injury patient advocates at CerebralPalsyHelp.org are alerting parents of children with cerebral palsy of new research information on the site. Duke University was recently awarded a research grant to explore the use of umbilical cord cells to treat brain damage causing cerebral palsy and other conditions*.

The CP Help Center is a national advocacy center providing the latest on cerebral palsy treatment, clinical trials, resources and litigation news. Parents can learn more about their childs condition and how it may have been caused, get information on available assistance, and decide if they should seek legal advice.

Cerebral palsy affects muscle movement, coordination and posture. It is the leading cause of functional and developmental disability in children in the United States**, occurring in approximately 3.3 out of every 1,000 births, and affecting approximately 500,000 children**.

While CP affects muscle function, it is actually a neurological disorder caused by brain damage to the parts that control muscle function***. This usually occurs before, during or after birth***.

Cerebral palsy may be caused by factors occurring to the fetus during pregnancy, or by trauma or asphyxiation during labor***. There is no cure at this time, however, researchers are working towards better treatments.

Now, the CP Help Center has learned that Duke Medical Center has received a $15 million grant from the Marcus Foundation to begin two years of umbilical cord stem cell research, in what is eventually expected to become a five-year, $41 million study*.

Duke researchers will study whether cord blood can help repair dysfunctional or damaged parts of the brain and hope to develop cell-based therapies that could help millions affected by cerebral palsy, stroke or autism*. The study will include approximately 100 children with cerebral palsy, in trials that inject donated cord blood to treat their brain damage*.

Anyone whose child has been diagnosed with cerebral palsy should learn more about how their condition was caused, or speak with a lawyer about their legal options. The CP Help Center only recommends lawyers who specialize in cerebral palsy lawsuits.

For more information on the research, treatment, causes and litigation news related to cerebral palsy, or to speak with a lawyer, visit http://www.cerebralpalsyhelp.org today.

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CP Help Center Adds New Information About Cerebral Palsy Cord Blood Research

In your bones, there is fat.

Why? Researchers don't know, but they have theories.

How does it get there? They have theories about that, too.

Is it the same sort of fat found in muscle? Not sure.

Is this bone fat a bad thing? Yes. Researchers think it is. But sometimes, they say, it might not be so bad.

"This is a new field," said Maya Styner, MD, an assistant professor of medicine in the University of North Carolina School of Medicine. "We don't know exactly how it's produced or why it's there to begin with. There are a lot of unanswered questions."

But Styner, an endocrinologist, has used a new kind of imaging technique to answer at least two: what do diabetes drugs and exercise -- or the lack of it -- do to bone fat, and why does this matter?

Stains and scans

Our bones are not stagnant, rock-like things. They change. Marrow -- the tissue inside bones -- is full of various kinds of cells. And marrow is also full of fat. The amounts of these cells and fats can decrease or increase over time. And the production of these marrow cells and fat depend on a specific type of progenitor cell called a mesenchymal stem cell.

"These stem cells give rise to both bone and fat," Styner said. "For a long time in the bone world, it's been thought that these stem cells produce bone but then, as we age, they start to produce fat, instead."

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Fat of the bone: Exercise, diabetes affect amount of fat inside bones

PUBLIC RELEASE DATE:

16-Jun-2014

Contact: David Ruth david@rice.edu 713-348-6327 Rice University

HOUSTON (June 16, 2014) How does a stem cell decide what path to take? In a way, it's up to the wisdom of the crowd.

The DNA in a pluripotent stem cell is bombarded with waves of proteins whose ebb and flow nudge the cell toward becoming blood, bone, skin or organs. A new theory by scientists at Rice University shows the cell's journey is neither a simple step-by-step process nor all random.

Theoretical biologist Peter Wolynes and postdoctoral fellow Bin Zhang set out to create a mathematical tool to analyze large, realistic gene networks. As a bonus, their open-access study to be published this week by the Proceedings of the National Academy of Sciences helped them understand that the process by which stem cells differentiate is a many-body problem.

"Many-body" refers to physical systems that involve interactions between large numbers of particles. Scientists assume these many bodies conspire to have a function in every system, but the "problem" is figuring out just what that function is. In the new work, these bodies consist not only of the thousands of proteins expressed by embryonic stem cells but also DNA binding sites that lead to feedback loops and other "attractors" that prompt the cell to move from one steady state to the next until it reaches a final configuration.

To test their tool, the researchers looked at the roles of eight key proteins and how they rise and fall in number, bind and unbind to DNA and degrade during stem cell differentiation. Though the interactions may not always follow a precise path, their general pattern inevitably leads to the desired result for the same reason a strand of amino acids will inevitably fold into the proper protein: because the landscape dictates that it be so.

Wolynes called the new work a "stylized," simplified model meant to give a general but accurate overview of how cell networks function. It's based on a theory he formed in 2003 with Masaki Sasai of Nagoya University but now takes into account the fact that not one but many genes can be responsible for even a single decision in a cellular process.

"This is what Bin figured out, that one could generalize our 2003 model to be much more realistic about how several different proteins bind to DNA in order to turn it on or off," Wolynes said.

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Many bodies prompt stem cells to change

Stratford, CT (PRWEB) June 24, 2014

Consumers should be aware of four things before buying skin care which are the ingredients, the formulation and the science to support the claims. The final thing they should notice are the results.

It had been several years since the anti-aging category had skyrocketed. Women are realizing that they can indeed skip the invasive procedures and reverse the signs of premature ageing skin with the help of a few bottles and jars. Theres just one catch, theyre just not bottles and jars; its Innarah. Innarah is the skin care collection that will change the way women feel about their skin.

Innarah is the first ever formulated skin care that works with the skins immune system.

Mr. Manzoor H. Jaffery, CEO Innarah Inc. has formulated a unique technology known as biofermentation. Mr. Jaffery perfected these fermented, anti-aging formulas and signature VenoDefense collection, which replicates the effects of snake venom using a botanical base with cutting edge ingredients such as Elk Antler Velvet, Ormus Gold, Plant Stem Cells and Marine Phytoplankton.

After being dissatisfied with so many skin care products on the market, Mr. Jaffery wanted something that really worked. Jaffery developed a process called Bioferm that is modelled on the ancient alchemic process called Nigredo, whose sole purpose is to transform the life force within matter. This process is actually different from other product formulations where the trick is their blending process. So, in essence, because Innarahs ingredients are fermented, there is no danger of the ingredients going through an oxidation process; plus, the result is a much more powerful cream.

As Jaffery explains, The ingredients are powerful, just like raw food. It helps with the skins own immune system. Many might dismiss this as hogwash, but listen to the science behind this for a bit. Because the skin is the largest organ in the body, and is the first line of defense in the immune system, its imperative to help protect it. This is why people recommend to eat daily fruits and vegetables.

Now, how can a skin care cream help with the immune system? It all has to do with the reticulation of Langerhans Cells, which are white blood cells generated in the bone marrow, Jaffery goes on to say. When they arrive at the epidermis, they develop small legs or dendrites, and automatically generate an immune response to the skin when they come into contact with ingredients they dont recognize. But ingredients that have been through the biofermentation process are readily accepted by these cells, so in essence Innarah acts as a bio catalyst.

Innarah is one of the few companies that offers an Oxygenated Crme that helps the healing of adult acne, cold sores, hyperpigmentation and other skin issues. Using Innarah products also aid the skin by diffusing and removing under eye puffiness and inflammation.

Innarah is for any skin color or gender and is recommended for people between 25-85 years old. Innarah is for that glow from-within associated with youth.

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The Discovery of a Unique Skincare System Which Acts as Food for the Skin and Absorb Immediately Reducing the ...

San Diego is buzzing about biotech this week: The BIO International Convention is in town at the San Diego Convention Center. While the conference has drawn big names like entrepreneur Sir Richard Branson and former Secretary of State Hillary Clinton as its keynote speakers, it's not just the guests who are making headlines.

Companies are announcing new ventures and clinical trials on a wide range of bio-tech topics, including regenerative medicine and stem cells.

A popular method now being used by stem cell researchers is known as "disease in a dish." The process uses a patient's own skin cells and manipulates them into stem cells. The cells are then tested with drug combinations right in the Petri dish to determine if they might assist with a condition or disease. But even though these cells, known as IPS cells, are not controversial embryonic cells, ethical questions about their use remain.

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BIO Convention Puts Spotlight On San Diego Stem-Cell Research

Alzheimer #39;s Disease Prevention and Treatment
http://www.placidway.com/subtreatment-detail/treatment,31,subtreatment,256.html/Alzheimers-Disease-Stem-Cell-Therapy--Treatment-Abroad - Watch this educational video about Alzheimer #39;s disease...

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Alzheimer's Disease Prevention and Treatment - Video

PUBLIC RELEASE DATE:

17-Jun-2014

Contact: Vera Siegler vera.siegler@tum.de 49-892-892-2731 Technische Universitaet Muenchen

This news release is available in German.

The cells of the human immune system are created from special stem cells in the bone marrow. In diseases affecting the bone marrow, such as leukemia, the degenerate cells must be destroyed using radiation or chemotherapy. Subsequently, the hematopoietic system has to be replaced with stem cells from the blood of a healthy donor. Because of the resulting temporary weakening of the immune system, patients are more exposed to viruses that would normally be warded off.

The cytomegalovirus (CMV), which can cause serious damage to lungs or liver in persons with a weakened defense, poses a major clinical problem. In healthy human beings, a CMV infection will usually not produce any symptoms, since the virus is kept at bay by specific immune cells. In their work, the scientists were able to demonstrate that the transfer of just a few specific immune cells is sufficient to protect the recipient with the weakened immune system against infections. To do this, they used T cells that can recognize and kill specific pathogens.

Tested in an animal model

Dr. Christian Stemberger, first author of the study, and his colleagues, first isolated T cells from the blood of healthy donor mice. These immune cells were directed against molecular elements of a bacterial species which normally causes severe infections in animals. The T cells were then transferred to recipient mice that, due to a genetic modification, could no longer produce immune cells of their own similarly to patients suffering from leukemia.

Following the T cell transfer, the researchers infected the treated recipient mice with the bacteria. The results showed that the animals now have effective immune protection against the pathogens, preventing them from becoming ill. "The most astonishing result was that the offspring cells of just one transferred donor cell were enough to completely protect the animals," Christian Stemberger explains.

Successfully used in patients

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Promising T cell therapy

Stem cells have the unique ability to become any type of cell in the body. Given this, the possibility that they can be cultured and engineered in the laboratory makes them an attractive option for regenerative medicine. However, some conditions that are commonly used for culturing human stem cells have the potential to introduce contaminants, thus rendering the cells unusable for clinical use. These conditions cannot be avoided, however, as they help maintain the pluripotency of the stem cells.

In a study published in Scientific Reports, a group from the RIKEN Center for Life Science Technologies in Japan has gained new insight into the role of CCL2, a chemokine known to be involved in the immune response, in the enhancement of stem cell pluripotency. In the study, the researchers replaced basic fibroblast growth factor (bFGF), a critical component of human stem cell culture, with CCL2 and studied its effect. The work showed that CCL2 used as a replacement for bFGF activated the JAK/STAT pathway, which is known to be involved in the immune response and maintenance of mouse pluripotent stem cells. In addition, the cells cultured with CCL2 demonstrated a higher tendency of colony attachment, high efficiency of cellular differentiation, and hints of X chromosome reactivation in female cells, all markers of pluripotency.

To understand the global effects of CCL2, the researchers compared the transcriptome of stem cells cultured with CCL2 and those with bFGF. They found that stem cells cultured with CCL2 had higher expression of genes related to the hypoxic response, such as HIF2A (EPAS1). The study opens up avenues for further exploring the relationship between cellular stress, such as hypoxia, and the enhancement of pluripotency in cells. Yuki Hasegawa of CLST, who led the study, says, "Among the differentially expressed genes, we found out that the most significantly differentially expressed ones were those related to hypoxic responses, and hypoxia is known to be important in the progression of tumors and the maintenance of pluripotency. These results could potentially contribute to greater consistency of human induced pluripotent stem cells (iPSCs), which are important both for regenerative medicine and for research into diseases processes."

As a way to apply CCL2 towards the culturing of human iPSCs with more consistent quality, the researchers developed dishes coated with CCL2 and LIF protein beads. This allowed stem cells to be cultured in a feeder-free condition, preventing the risk that viruses or other contaminants could be transmitted to the stem cells. While the exact mechanisms of how CCL2 enhances pluripotency has yet to be elucidated, this work highlights the usefulness of CCL2 in stem cell culture.

Story Source:

The above story is based on materials provided by RIKEN. Note: Materials may be edited for content and length.

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Pushing cells towards a higher pluripotency state

PUBLIC RELEASE DATE:

19-Jun-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

Stroke is a leading cause of death and disability in developed countries, and there is an urgent need for more clinically effective treatments. A study published by Cell Press June 19th in Stem Cell Reports reveals that simultaneous transplantation of neural and vascular progenitor cells can reduce stroke-related brain damage and improve behavioral recovery in rodents. The stem cell-based approach could represent a promising strategy for the treatment of stroke in humans.

"Our findings suggest that early cotransplantation treatment can not only replace lost cells, but also prevent further deterioration of the injured brain following ischemic stroke," says senior study author Wei-Qiang Gao of Shanghai Jiaotong University. "With the development of human embryonic and induced pluripotent stem cell technology, we are optimistic about the potential translation of our research into clinical use."

The most common kind of stroke, known as ischemic stroke, is caused by a blood clot that blocks or plugs a blood vessel in the brain. Although a medicine called tissue plasminogen activator can break up blood clots in the brain, it must be given soon after the start of symptoms to work, and there are no other clinically effective treatments currently available for this condition. Stem cell transplantation represents a promising therapeutic strategy, but transplantation of either neural progenitor cells or vascular cells has shown restricted therapeutic effectiveness.

In the new study, Gao teamed up with colleagues at Shanghai Jiao Tong University, including Jia Li, Yaohui Tang, and Guo-Yuan Yang, to test whether cotransplantation of both neural and vascular precursor cells would lead to better outcomes. They induced ischemic stroke in rats and then simultaneously injected neural and vascular progenitor cells from mice into the stroke-damaged rat brains 24 hours later. The transplanted precursor cells turned into all major types of vascular and brain cells, including mature, functional neurons. The resulting vascular cells developed into microvessels, while the grafted neural cells produced molecules known to stimulate the growth of both neurons and vessels.

"This is the first study to use embryonic stem cell-derived vascular progenitor cells together with neural progenitor cells to treat ischemic stroke," Gao says. "These two types of progenitors generate nearly all types of brain cells, including endothelial cells, pericytes/smooth muscle cells, neurons, and astrocytes, resulting in better restoration of neurovascular units and better replacement of the lost cells in the stroke model. A previously reported cotransplantation approach published in the journal Stem Cells in 2009 (doi: 10.1002/stem.161) was limited because it did not use vascular precursor cells capable of turning into all major types of vascular cells important for recovery. Our findings here suggest that cotransplantation of the two types of cells that restore the neurovascular unit more effectively is a better approach for the treatment of ischemic stroke."

Two weeks after stroke, rats that had undergone cotransplantation showed less brain damage and improved behavioral performance on motor tasks compared with rats that had been treated with neural progenitor cells alone. "Our findings suggest that cotransplantation of neural and vascular cells is much more effective than transplantation of one cell type alone because these two cell types mutually support each other to promote recovery after stroke," Gao says.

###

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Stem cell-based transplantation approach improves recovery from stroke

PUBLIC RELEASE DATE:

12-Jun-2014

Contact: Hannah Postles h.postles@sheffield.ac.uk 01-142-221-046 University of Sheffield

A time-lapse study of human embryonic stems cells has identified bottlenecks restricting the formation of colonies, a discovery that could lead to improvement in their use in regenerative medicine.

Biologists at the University of Sheffield's Centre for Stem Cell Biology led by Professor Peter Andrews and engineers in the Complex Systems and Signal Processing Group led by Professor Daniel Coca studied human pluripotent stem cells, which are a potential source of cells for regenerative medicine because they have the ability to produce any cell type in the body.

However, using these stem cells in therapies is currently hampered by the fact they can acquire genetic changes during prolonged culture which are non-random and resemble mutations in cancer cells.

Researchers used time-lapse imaging of single human embryonic stem cells to identify aspects of their behaviour that restrict growth and would be targets for mutations that allow cells to grow more efficiently.

Dr Ivana Barbaric, from the University of Sheffield's Department of Biomedical Science, said: "We study pluripotent stem cells, which have huge potential for use in regenerative medicine due to their ability to become any cell in the human body. A pre-requisite for this is maintaining large numbers of undifferentiated cells in culture. However, there are several obstacles such as cells tend to die extensively during culturing and they can mutate spontaneously. Some of these genetic mutations are known to provide stem cells with superior growth, allowing them to overtake the culture a phenomenon termed culture adaptation, which mimics the behaviour of cancer cells.

"In order for pluripotent stem cells to be used safely in regenerative medicine we need to understand how suboptimal culture conditions, for example culturing cells at low split ratios, affect the cells and can lead to culture adaptation."

The team's research combined the use of time-lapse microscopy, single-cell tracking and mathematical modelling to characterise bottlenecks affecting the survival of normal human embryonic stem cells and compared them with adapted cells.

Read more from the original source:
Time-lapse study reveals bottlenecks in stem cell expansion

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