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CSU research on horse injuries, stem-cell recovery, may help humans

By Stem Cell Treatment

Doctors, nurses and anesthesiologist's care for a horse that will be receiving stem cells to help repair a meniscal tear in the stifle at the CSU Veterinary Teaching Hospital in Fort Collins. (Joe Amon, The Denver Post)

Stem-cell research by Colorado State University staffers using bone marrow from horses to heal joint injuries on the same animal is making strides, and researchers have great hope that the project will lead to human medical applications.

A team with CSU's Equine Orthopaedic Research Center reports that adding stem-cell therapy to traditional arthroscopic surgery on horses has significantly increased success rates.

Horses that had follow-up, stem-cell treatment were twice as likely to return to normal activity as those that did not, said David Frisbie, an associate professor of equine surgery with CSU and part of the research team.

"We've doubled it, conservatively," in treating cartilage damage in the knee, Frisbie said.

The team had results of its work published last year in the journal Veterinary Surgery.

Some lesions in the meniscus of horses that could not be treated by surgery have been successfully mended using stem cells alone.

"Western performance horses, reining and cutting horses, and barrel horses are very prone to meniscal injuries," Frisbie said.

Beyond meniscus damage, researchers also have focused on tendon lesions in the lower leg, which typically strike race horses.

Horses that suffered a tendon lesion had about a 66 percent chance of reinjury after surgery. Add stem-cell treatment and the reinjury rate drops to 21 percent, Frisbie said.

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CSU research on horse injuries, stem-cell recovery, may help humans

Quadriplegic veteran to receive stem cell treatments

By Stem Cell Doctors

LAWTON, Okla._A stem cell surgery procedure, not yet approved by the FDA, could give a local paralyzed veteran the use of his arms again.

Two years ago, retired Senior Airman Ted "TJ" Williams was left as a quadriplegic when his Humvee rolled over in a freak accident while on duty in Montana. He spent several weeks in a coma.

Now, he and his wife have found a surgery that may improve his physical abilities. They're dipping into their funds to pay for the procedure, since it's not covered by insurance, but they've set up a GoFundMe account to raise $7,500 to cover travel expenses out of the country to get the treatment.

Williams is able to move his left wrist and arm more, and has even gained more core control, thanks to therapy. But, he still needs his wife's help for simple tasks like getting dressed and using the restroom.

Williams sits next to his wife in his wheelchair and watches TV. Years ago, he would've been running outside, but one accident changed everything.

"I just remember leaving base and then waking up 2 or 3 weeks later, wondering where am I. I couldn't move anything. It was just shocking seeing my family around my bed. I was just like, Wow. What's going on,'" recalled Williams.

On November 29, 2012, Williams was on duty with his security forces team. He was in the back seat when his Humvee suddenly swerved to miss a herd of deer, rolling several times. He was ejected from the vehicle and was later found 60 feet away.

Williams was rushed to the hospital. When he woke up from the coma, doctors told him he had broken the vertebrae in his neck and lost function from the chest down.

"I was really upset and scared. Me and my wife are young. We haven't had children yet or anything. It scared me not knowing what the future was to hold," said Williams.

He was sent to a VA hospital in San Antonio for in-patient rehab. Once he was finished, he met a physical trainer in who specializes in exercises for those who are suffering from spinal cord and other neurological injuries, which was just what he needed.

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Quadriplegic veteran to receive stem cell treatments

Bad luck may play a role in two thirds of cancers

By Stem Cell Medical Center

While environmental factors and genetics play a role in the development of cancer, scientists at Johns Hopkins University have used statistical modeling to show that two-thirds of adult cancers may be attributable to "bad luck," or random mutations, rather than lifestyle.

Researchers Bert Vogelstein M.D. (Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute) and Cristian Tomasetti PhD (assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health) charted the number of stem cell divisions in 31 tissue types and compared them with the lifetime risks of cancer in the same tissues among Americans.

Stem cells "self-renew," meaning they repopulate cells that die off in a specific organ. Cancer occurs when tissue-specific stem cells make random mistakes, or mutations.The more mutations, the higher the risk of cancer, however it was not previously known how these random mutations contribute to cancer compared to genetic or environmental factors.

"All cancers are caused by a combination of bad luck, the environment and heredity, and weve created a model that may help quantify how much of these three factors contribute to cancer development," says Vogelstein.

Vogeltsein and Tomasetti determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated. Using statistical theory, they calculated that approximately 65 percen of the variation in cancer risk can be explained by the number of stem cell divisions.

Of the pair tissue types studied, the researchers found that 22 cancer types, including head and neck, esophageal, gallbladder and some bone cancers, can be largely explained by the bad luck factor of random DNA mutations during cell division.

The other nine cancer types had incidences higher than predicted by bad luck, so are presumably due to a combination of bad luck as well as environmental or genetic factors. These include lung cancer, which is linked to smoking, and skin cancer, which is linked to sun exposure.

Vogelstein and Tomasetti use the analogy of a car accident to help explain their results. "Our results would be equivalent to showing a high correlation between length of trip and getting into an accident," they say. "The longer the trip is, the higher the risk of an accident."

They liken road conditions en-route to the destination to the environmental factors in cancer. Worse conditions are associated with a higher risk of an accident. The mechanical condition of the car is a metaphor for inherited genetic factors. Mechanical problems in the car, such as bad brakes and worn tires, increase the risk of an accident. The more mechanical defects, the greater the risk. Similarly, the amount of inherited genetic mutations contributes to cancer risk.

The length of the trip can be compared to the stem cell divisions and random mutations Vogelstein and Tomasetti discuss in their paper. Regardless of road and car conditions, the probability of an accident increases with distance traveled. Short trips have the lowest risk, while long trips are associated with the highest risk.

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Bad luck may play a role in two thirds of cancers

New Technology from Asymmetrex Promises to End the Era of Elusive Adult Tissue Stem Cells

By Stem Cell Medicine

Boston, MA (PRWEB) January 08, 2015

James Sherley, Director of the new biotech start-up Asymmetrex, LLC (previously, the Adult Stem Cell Technology Center, LLC) says that he is looking forward to laboratories around the globe evaluating the companys most recent exciting new stem cell technology, which allows tissue stem cells to be counted for the first time. The new technology is reported online this week in Stem Cell Research.

With only the purchase of two commercially available antibodies, any basic cell biology lab can evaluate the new technology for counting its favorite adult tissue stem cells, which Asymmetrex also refers to as distributed stem cells. Asymmetrex scientists accomplished the essential proof of principle in the report with cultured mouse hair follicle stem cells. They also showed that cells with the specific detection criterion were found in mouse hair follicles themselves in regions known to contain the stem cells. With collaborator Dr. Jennifer Chen, they demonstrated that cells in experimental cultures enriched for human skeletal muscle stem cells had the criterion, too. The technology is predicted to be universally able to count adult tissue stem cells in many different tissue types and different vertebrate species, including most, if not all, human tissues.

To count tissue stem cells, the first antibody needed is one that identifies chromosomes found in all cells about an hour before they divide to become two cells. The second antibody needed is one that identifies a special set of chromosomes that is found specifically in adult tissue stem cells. Asymmetrexs Director Sherley spent the last 16 years defining properties of these unique chromosomes, which are called immortal chromosomes. By evaluating both of these antibodies cell detection patterns simultaneously, adult tissue stem cells can be identified with sufficient specificity to count them with a high degree of confidence.

The new report shows that getting to the new technology was a rather complicated business. The project started with the work of Dr. Minsoo Noh when he was a doctoral graduate student in Dr. Sherleys lab at the Massachusetts Institute of Technology. In his graduate studies, Dr. Noh applied a bioengineering-bioinformatics approach to identifying genes that were highly associated with the unique properties of adult tissue stem cells. To avoid the previously unsolved problem of impure tissue stem cells, Dr. Noh used a family of cells that were engineered to model the unique properties of tissue stem cells. He was successful in identifying a large number of cellular genes whose expression was highly specific for unique tissue stem cell properties.

With Dr. Nohs success, the research team now faced a common bioinformatics pitfall too many genes to know which to study next. Dr. David Winklers group at CSIRO in Australia, co-authors of the report, provided a solution. The new report details how Winklers team applied a newly emerging probabilistic approach to reduce a thousand-plus member gene set down to a single gene for interrogation, the histone H2A variant H2A.Z. Oddly, H2A.Z was reduced during adult tissue stem cell specific functions, which went against the conventional biomarker concept of being increased. Dr. Yang Hoon Huh, then a post-doctoral fellow with the Sherley team, undertook an intent investigation of H2A.Zs tissue stem cell-associated properties despite its non-conformist expression. Due to his persistent studies, H2A.Z emerged as the key target of the second antibody in the new technology.

The ability to identify adult tissue stem cells specifically means that now, for the first time, they can be counted. This long awaited capability will begin a new era of quantitative stem cell biology and stem cell medicine. Sherley predicts that, It will be as if tissue stem cell biology put on glasses for the first time. Previously, tissue stem cell research, existing stem cell medicine (e.g., bone marrow transplantation), and new regenerative medicine developments have operated in a blurry world of not knowing the actual number of the elusive tissue stem cells involved in experiments or transplantation treatments. The ability simply to count the critical cells will have a major impact on the quality and progress of these important applications for continuing advances in medicine and human health.

******************************************************************************************** Asymmetrex, LLC is a Massachusetts life sciences company. Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D. is the foremost authority on the unique properties of adult tissue stem cells. The companys patent portfolio contains biotechnologies that solve the three main technical problems production, quantification, and monitoring that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells. Currently, Asymmetrex is employing its technological advantages to pursue commercialization of facile methods for monitoring adult tissue stem cell number and function.

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New Technology from Asymmetrex Promises to End the Era of Elusive Adult Tissue Stem Cells

Gamida Cell's NiCord gets FDA and EMA orphan drug status

By Uncategorized

Published 07 January 2015

Gamida Cell, a leader in cell therapy technologies and products for transplantation and adaptive immune therapy, announced that orphan drug designation has been granted by The US Department of Health and Human Services, The FDA Office of Orphan Products Development (OOPD) for the investigational medicinal product NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma and myelodysplastic syndrome (MDS).

The FDA orphan drug designation coincides with the positive opinion of the European Medicines Agency's (EMA's) Committee for Orphan Medicinal Products (COMP) regarding NiCord as a treatment for AML. Gamida Cell intends to file for NiCord orphan drug status with the EMA for other indications as well.

"Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell's commercialization plans a major step further, as both afford significant advantages. We very much appreciate the positive feedback and support of the FDA and EMA and look forward to continuing what has been a very positive dialogue with these important agencies," said Gamida Cell president and CEO Dr. Yael Margolin.

The FDA and EMA grant an orphan drug designation to promote the development of products that demonstrate promise for the treatment of rare diseases or conditions. Orphan drug designation provides for various regulatory and economic benefits, including seven years of market exclusivity in the U.S. and 10 years in the EU.

NiCord is derived from a single cord blood unit which has been expanded in culture and enriched with stem cells using Gamida Cell's proprietary NAM technology.

It is currently being tested in a Phase I/II study as an investigational therapeutic treatment for hematological malignancies such as leukemia and lymphoma. In this study, NiCord is being used as the sole stem cell source.

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Gamida Cell's NiCord gets FDA and EMA orphan drug status

Cord Blood Banking Leader, Cryo-Cell International, Continues to Support the Advancement of Regenerative Medicine

By Uncategorized

Tampa, FL (PRWEB) January 06, 2015

One million Americans experience acute myocardial infarctions, commonly known as a heart attack, each year and of those, approximately 300,000 to 500,000 individuals develop heart failure. A heart attack occurs when blood stops flowing properly to a part of the heart and the heart muscle is injured and can die because it is not receiving enough oxygen.

Cryo-Cell International has agreed to provide the Center with cord blood collections that have previously been donated to Cryo-Cell International by parents and designated for research use to advance regenerative medicine. These cord blood collections will allow the Centers scientists to continue to investigate the mechanisms whereby stem cells can be beneficial in limiting damage from heart attacks. A team at the Center, led by researcher and cardiology specialist, Robert J. Henning, M.D., has demonstrated in research animals that stem cells obtained from human umbilical cord blood can release a large number of biologically active growth factors and anti-inflammatory chemicals that can limit the substantial heart inflammation, cell injury and cell destruction that occurs with acute heart attacks, significantly reducing the effects of heart attacks, even when administered up to 24 hours after the heart attack.

We are making good progress in our studies thanks to the cord blood stem cells contributed by Cryo-Cell International, reports Henning.

Cryo-Cell International and others have demonstrated that human umbilical cord blood stem cells can be preserved for more than 20 years without loss of cell viability or potency. Consequently, parents who have the foresight to use cord blood banking services upon their babys birth can potentially use these cord blood stem cells years later to provide a regenerative treatment for a family member if an acute heart attack occurs. The Centers scientists hope to bring umbilical cord blood stem cell therapy to the treatment of patients who have experienced heart attacks within the next five years.

Heart disease is still the number one leading cause of death in the United States. We feel very fortunate that we can provide a valuable and consistent source of cord blood banked stem cells to the Center for Cardiovascular Research, said David Portnoy, Chairman and Co-CEO of Cryo-Cell International.

About Cryo-Cell International

Founded in 1989, Cryo-Cell International, Inc. is the world's first and most highly accredited private cord blood bank. More than 500,000 parents from 87 countries trust Cryo-Cell International to preserve their family members' stem cells. Cryo-Cell International's mission is to provide clients with state-of-the-art stem cell cryopreservation services and support the advancement of regenerative medicine. Cryo-Cell International operates in a facility that is FDA registered, cGMP-/cGTP-compliant and is licensed in all states requiring licensure. In addition to earning AABB accreditation for cord blood banking, Cryo-Cell International is also the first U.S. (for private use only) cord blood bank to receive FACT accreditation for voluntarily adhering to the most stringent cord blood quality standards set by any internationally recognized, independent accrediting organization. Cryo-Cell International is ISO 9001:2008 certified by BSI, an internationally recognized, quality assessment organization. Cryo-Cell International is a publicly traded company, OTCQB: CCEL. For more information, please visit http://www.Cryo-Cell.com.

About the University of South Florida Center for Cardiovascular Research

The University of South Florida Morsani College of Medicines Cardiovascular Services Research Unit has been in existence for almost 20 years and evaluates pharmacotherapeutic agents and the latest treatment and devices for cardiovascular disease.

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Cord Blood Banking Leader, Cryo-Cell International, Continues to Support the Advancement of Regenerative Medicine

Circadian rhythms regulate skin stem cell metabolism and expansion, study finds

By Uncategorized

UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

Andersen adds that it is possible that future studies could advance therapeutic insights from this research.

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Circadian rhythms regulate skin stem cell metabolism and expansion, study finds

Circadian rhythms regulate skin stem cell metabolism and expansion, UCI study finds

By Uncategorized

Body clock protects cells from metabolism-generated oxygen radical damage during division

Irvine, Calif., Jan. 6, 2015 -- UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

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Circadian rhythms regulate skin stem cell metabolism and expansion, UCI study finds

Gamida Cell treatment granted orphan drug status

By Stem Cell Treatment

Stem cell therapy developer Gamida Cell has been awarded orphan drug status by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for leukemia treatment NiCord. The investigational drug treats acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma and myelodysplastic syndrome (MDS). Gamida Cell intends to file for NiCord orphan drug status with the EMA for other indications as well.

Gamida Cell president and CEO Dr. Yael Margolin said, "Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell's commercialization plans a major step further, as both afford significant advantages. We very much appreciate the positive feedback and support of the FDA and EMA and look forward to continuing what has been a very positive dialogue with these important agencies."

The FDA and EMA grant an orphan drug designation to promote the development of products that demonstrate promise for the treatment of rare diseases or conditions. Orphan drug designation provides for various regulatory and economic benefits, including seven years of market exclusivity in the US and 10 years in the EU.

NiCord is derived from a single cord blood unit, which has been expanded in culture and enriched with stem cells using Gamida Cell's proprietary NAM technology. It is currently being tested in a Phase I/II study as an investigational therapeutic treatment for hematological malignancies such as leukemia and lymphoma. In this study, NiCord is being used as the sole stem cell source.

Published by Globes [online], Israel business news - http://www.globes-online.com - on January 6, 2015

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Gamida Cell treatment granted orphan drug status

'CRISPR' science: Newer genome editing tool shows promise in engineering human stem cells

By Stem Cell Medicine

Johns Hopkins study could advance use of stem cells for treatment and disease research

A powerful "genome editing" technology known as CRISPR has been used by researchers since 2012 to trim, disrupt, replace or add to sequences of an organism's DNA. Now, scientists at Johns Hopkins Medicine have shown that the system also precisely and efficiently alters human stem cells.

In a recent online report on the work in Molecular Therapy, the Johns Hopkins team says the findings could streamline and speed efforts to modify and tailor human-induced pluripotent stem cells (iPSCs) for use as treatments or in the development of model systems to study diseases and test drugs.

"Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs for human therapy aren't that far away," says Zhaohui Ye, Ph.D., an instructor of medicine at the Johns Hopkins University School of Medicine. "This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells."

CRISPR originated from a microbial immune system that contains DNA segments known as clustered regularly interspaced short palindromic repeats. The engineered editing system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions far more efficiently than other gene editing techniques, such as TALEN, short for transcription activator-like effector nuclease.

Despite CRISPR's advantages, a recent study suggested that it might also produce a large number of "off-target" effects in human cancer cell lines, specifically modification of genes that researchers didn't mean to change.

To see if this unwanted effect occurred in other human cell types, Ye; Linzhao Cheng, Ph.D., a professor of medicine and oncology in the Johns Hopkins University School of Medicine; and their colleagues pitted CRISPR against TALEN in human iPSCs, adult cells reprogrammed to act like embryonic stem cells. Human iPSCs have already shown enormous promise for treating and studying disease.

The researchers compared the ability of both genome editing systems to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another. As model genes, the researchers used JAK2, a gene that when mutated causes a bone marrow disorder known as polycythemia vera; SERPINA1, a gene that when mutated causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that's been recently discovered to be a "safe harbor" in the human genome for inserting foreign genes.

Their comparison found that when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all three gene systems, inducing up to 100 times more cuts. However, when using these genome editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs, the researchers report.

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'CRISPR' science: Newer genome editing tool shows promise in engineering human stem cells

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