Yearly Archives: 2015


Stem Cell Clinic > 2015

Scripps Health Receives $7.6M Grant to Regrow Knee Cartilage

By Stem Cell Clinic

Dr. Darryl DLima. Photo courtesy of Scripps Health

Scripps Health announced today it has received a $7.6 million grant to study the repair and regeneration of knee cartilage, and the underlying bone defects and lesions caused by osteoarthritis.

The award from the California Institute for Regenerative Medicine will support ongoing stem cell research by the Shiley Center for Orthopedic Research and Education at Scripps Clinic.

The funding provided by CIRM is essential to the development and support of the research we are doing with regard to tissue regeneration at Scripps, said Dr. Darryl DLima, the Scripps Health director of orthopedic research. With this grant we plan to continue our progress in this field and move toward clinical trials within the next three years.

Scripps researchers are studying a cell therapy that combines stem cells with a natural scaffold made of water-based gels to support the repair of cartilage and bone defects. Such defects, if left untreated, are a major factor in contributing to early osteoarthritis in patients younger than 55.

Caused by the deterioration of cartilage between joints, osteoarthritis affects more than 27 million people in the United States, according to the U.S. Centers for Disease Control and Prevention.

Almost all current strategies to repair knee cartilage involve the removal of healthy cartilage and tissue around the lesion and the creation of artificial defects in the joint to facilitate further treatment or implantation. However, for younger patients with severe arthritis or impending arthritis, there is no treatment that can prevent, cure or even slow the progression of this disease.

Scientists with The Scripps Research Institute and Sanford-Burnham Medical Research Institute are assisting with the project.

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Scripps Health Receives $7.6M Grant to Regrow Knee Cartilage

Possible progress against Parkinson's and good news for stem cell therapies

By Stem Cell Treatment

Brazilian researchers at D'OR Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) have taken what they describe as an important step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson's disease. Using an FDA approved substance for treating stomach cancer, Rehen and colleagues were able to grow dopamine-producing neurons derived from embryonic stem cells that remained healthy and functional for as long as 15 months after implantation into mice, restoring motor function without forming tumors.

Parkinson's, which affect as many 10 million people in the world, is caused by a depletion of dopamine-producing neurons in the brain. Current treatments include medications and electrical implants in the brain which causes severe adverse effects over time and fail to prevent disease progression. Several studies have indicated that the transplantation of embryonic stem cells improves motor functions in animal models. However, until now, the procedure has shown to be unsafe, because of the risk of tumors upon transplantation.

To address this issue, the researchers tested for the first time to pre-treat undifferentiated mouse embryonic stem cells with mitomycin C, a drug already prescribed to treat cancer. The substance blocks the DNA replication and prevents the cells to multiply out of control.

The researchers used mice modeled for Parkinson's. The animals were separated in three groups. The first one, the control group, did not receive the stem cell implant. The second one, received the implant of stem cells which were not treated with mitomycin C and the third one received the mitomycin C treated cells.

After the injection of 50,000 untreated stem cells, the animals of the second group showed improvement in motor functions but all of them died between 3 and 7 weeks later. These animals also developed intracerebral tumors. In contrast, animals receiving the treated stem cells showed improvement of Parkinson's symptoms and survived until the end of the observation period of 12 weeks post-transplant with no tumors detected. Four of these mice were monitored for as long as 15 months with no signs of pathology.

Furthermore, the scientists have also shown that treating the stem cells with mitomycin C induced a four-fold increase in the release of dopamine after in vitro differentiation.

"This simple strategy of shortly exposing pluripotent stem cells to an anti-cancer drug turned the transplant safer, by eliminating the risk of tumor formation," says the leader of the study Stevens Rehen, Professor at UFRJ and researcher at IDOR.

The discovery, reported on April in the journal Frontiers in Cellular Neuroscience, could pave the way for researchers and physicians to propose a clinical trial using pluripotent stem cells treated with mitomycin C prior to transplant to treat Parkinson's patients and also other neurodegenerative conditions.

"Our technique with mitomycin C may speed the proposal of clinical trials with pluripotent cells to several human diseases," says Rehen. "It is the first step to make this kind of treatment with stem cells possible."

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Possible progress against Parkinson's and good news for stem cell therapies

UCSDs Stem Cell Break Through Could Lead to Treatment for Type-1 Diabetes

By Stem Cell Treatment

A UC San Diego student examines a bacteria culture. Photo courtesy UCSD

Researchers at the UC San Diego School of Medicine announced Thursdaytheyve discovered why its so hard to use stem cells to make liver and pancreatic cells, and their findings could lead to new treatments for diseases such astype-1 diabetes.

It turns out that the chromosomes in laboratory stem cells open slowly over time, in the same sequence that occurs during embryonic development. It isnt until certain chromosomal regions have reached the open state that they are able to respond to added growth factors and become liver or pancreatic cells, the researchers said.

Our ability to generate liver and pancreatic cells from stem cells has fallen behind the advances weve made for other cell types, said Dr. Maike Sander, a professor of pediatrics and cellular and molecular medicine, and director of the Pediatric Diabetes Research Center at UCSD.

So we havent yet been able to do things like test new drugs on stem cell-derived liver and pancreatic cells, Sander said. What we have learned is that if we want to make specific cells from stem cells, we need ways to predict how those cells and their chromosomes will respond to the growth factors.

Researchers have focused on stem cells for treating disease because they can be altered into hundreds of types of cells.

According to UCSD, it sometimes takes up to seven carefully orchestrated steps of adding certain growth factors at specific times to coax stem cells into the desired cell type.

Sander said the study found that the chromosomal regions that need to open before a stem cell can fully differentiate are linked to regions where there are variations in certain disease states. That means if a genetic variation in someones chromosomal region doesnt open at the right time, they could be more susceptible to a disease affecting that cell type.

Herteam is now working to further investigate what role, if any, the chromosomal regions and their variations play in diabetes.

Researchers with the University of Pennsylvania, Penn State University and Ludwig Institute for Cancer Research assisted with the study, funded by the National Institutes of Health, California Institute for Regenerative Medicine, the Helmsley Charitable Trust and Juvenile Diabetes Research Foundation.

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UCSDs Stem Cell Break Through Could Lead to Treatment for Type-1 Diabetes

Kentucky Fan Gets Life-Saving Stem Cell Donation From Univ. of Wisconsin Student

By Stem Cell Treatment

This Saturday when the University of Kentucky basketball team faces off with the University of Wisconsin in the NCAA tournament semi-finals, die-hard Kentucky fan Scott Logdon may think twice about rooting against the Wisconsin Badgers.

Nearly two years ago, Logdon was given a life-saving donation of stem cells that helped combat his acute myeloid leukemia. The donor of those cells turned out to be 22-year-old Chris Wirz, a student at the University of Wisconsin.

Logdon, 44, learned the identity of his donor last April, more than a year after the stem cell treatment and just days after the University of Kentucky squeaked past the University of Wisconsin at the NCAA semi-finals with a score of 74 to 73.

Logdon remembers feeling mixed emotions when the Kentucky wildcats won. Later, when he found out about his donor, he joked, That must have been the Badger blood in me.

Courtesy Angela Logdon

PHOTO: Chris Wirz gave life saving stem cells to Scott Logdon, who was suffering from leukemia.

Logdons ordeal started in the fall of 2012, when he was diagnosed with acute myeloid leukemia after mistaking early symptoms for strep throat. Logdon said his doctors told him chemotherapy could only keep the cancer at bay. A full stem cell transplant would be needed to cure him of the deadly disease.

Logdons doctors hoped one of his two siblings might be a match, but neither was able to donate. Longons family and community rallied in the small town of Saldasia, Kentucky, and registered over 120 people who would be willing to donate stem cells or bone marrow.

But no one who registered was a good match for Logdon.

[The doctors] went to the national bone marrow registry to try and find the match, the father of four said. I had to go back to the hospital every 30 days [for] maintenance chemo; it was a very long wait.

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Kentucky Fan Gets Life-Saving Stem Cell Donation From Univ. of Wisconsin Student

New UC San Diego Findings Could Lead To Diabetes Treatment

By Stem Cell Treatment

Researchers at the UC San Diego School of Medicine announced today they've discovered why it's so hard to use stem cells to make liver and pancreatic cells, and their findings could lead to new treatments for diseases like type 1 diabetes.

It turns out that the chromosomes in laboratory stem cells open slowly over time, in the same sequence that occurs during embryonic development. It isn't until certain chromosomal regions have reached the open state that they are able to respond to added growth factors and become liver or pancreatic cells, the researchers said.

"Our ability to generate liver and pancreatic cells from stem cells has fallen behind the advances we've made for other cell types," said Dr. Maike Sander, a professor of pediatrics and cellular and molecular medicine, and director of the Pediatric Diabetes Research Center at UCSD.

"So we haven't yet been able to do things like test new drugs on stem cell-derived liver and pancreatic cells," Sander said. "What we have learned is that if we want to make specific cells from stem cells, we need ways to predict how those cells and their chromosomes will respond to the growth factors."

Researchers have focused on stem cells for treating disease because they can be altered into hundreds of types of cells.

According to UCSD, it sometimes takes up to seven carefully orchestrated steps of adding certain growth factors at specific times to coax stem cells into the desired cell type.

Sander said the study found that the chromosomal regions that need to open before a stem cell can fully differentiate are linked to regions where there are variations in certain disease states. That means if a genetic variation in someone's chromosomal region doesn't open at the right time, they could be more susceptible to a disease affecting that cell type.

His team is now working to further investigate what role, if any, the chromosomal regions and their variations play in diabetes.

Researchers with the University of Pennsylvania, Penn State University and Ludwig Institute for Cancer Research assisted with the study, funded by the National Institutes of Health, California Institute for Regenerative Medicine, the Helmsley Charitable Trust and Juvenile Diabetes Research Foundation.

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New UC San Diego Findings Could Lead To Diabetes Treatment

Dying teenager fighting cancer has just THREE MONTHS to find a bone marrow donor

By Stem Cell Doctors

A teenage cancer victim has been given just three months to find a bone marrow donor to save his life.

Sixteen year-old Omar Al Shaikh and his mum are desperate to find him a suitable stem cell match and as he is half Romanian, half Arabic, the hunt is more difficult, the Birmingham Mail reports.

His mum Mirabela, 38, who sleeps at his hospital bedside has called for people to join the Anthony Nolan register to help.

I keep crying. He says, stop it, I dont want you to cry any more.

"I am the only parent and I have to be strong, Mirabella said.

Hopes: Omar Al Shaikh, with his mum Mirabela, wants to go to college

Finding a donor is very difficult. Because I am Romanian and Omars father is Arabic, it is a mixture between light and dark.

Omar was diagnosed with acute myeloid leukaemia after passing-out during a football match last Easter.

They told me it may be leukaemia, recalled Subway worker Mirabela.

I shouted, dont tell me that. You dont want to hear that.

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Dying teenager fighting cancer has just THREE MONTHS to find a bone marrow donor

Premature aging of stem cell telomeres, not inflammation, linked to emphysema

By Stem Cell Medicine

Lung diseases like emphysema and pulmonary fibrosis are common among people with malfunctioning telomeres, the "caps" or ends of chromosomes. Now, researchers from Johns Hopkins say they have discovered what goes wrong and why.

Mary Armanios, M.D., an associate professor of oncology at the Johns Hopkins University School of Medicine., and her colleagues report that some stem cells vital to lung cell oxygenation undergo premature aging -- and stop dividing and proliferating -- when their telomeres are defective. The stem cells are those in the alveoli, the tiny air exchange sacs where blood takes up oxygen.

In studies of these isolated stem cells and in mice, Armanios' team discovered that dormant or senescent stem cells send out signals that recruit immune molecules to the lungs and cause the severe inflammation that is also a hallmark of emphysema and related lung diseases.

Until now, Armanios says, researchers and clinicians have thought that "inflammation alone is what drives these lung diseases and have based therapy on anti-inflammatory drugs for the last 30 years."

But the new discoveries, reported March 30 in Proceedings of the National Academy of Sciences, suggest instead that "if it's premature aging of the stem cells driving this, nothing will really get better if you don't fix that problem," Armanios says.

Acknowledging that there are no current ways to treat or replace damaged lung stem cells, Armanios says that knowing the source of the problem can redirect research efforts. "It's a new challenge that begins with the questions of whether we take on the effort to fix this defect in the cells, or try to replace the cells," she adds.

Armanios and her team say their study also found that this telomere-driven defect leaves mice extremely vulnerable to anticancer drugs like bleomycin or busulfan that are toxic to the lungs. The drugs and infectious agents like viruses kill off the cells that line the lung's air sacs. In cases of telomere dysfunction, Armanios explains, the lung stem cells can't divide and replenish these destroyed cells.

When the researchers gave these drugs to 11 mice with the lung stem cell defect, all became severely ill and died within a month.

This finding could shed light on why "sometimes people with short telomeres may have no signs of pulmonary disease whatsoever, but when they're exposed to an acute infection or to certain drugs, they develop respiratory failure," says Armanios. "We don't think anyone has ever before linked this phenomenon to stem cell failure or senescence."

In their study, the researchers genetically engineered mice to have a telomere defect that impaired the telomeres in just the lung stem cells in the alveolar epithelium, the layer of cells that lines the air sacs. "In bone marrow or other compartments, when stem cells have short telomeres, or when they age, they just die out," Armanios says. "But we found that instead, these alveolar cells just linger in the senescent stage."

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Premature aging of stem cell telomeres, not inflammation, linked to emphysema

Key Mechanism Identified in Pediatric Bone Cancers That Allows Proliferation of Tumor-Forming Stem Cells

By Stem Cell Medical Center

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Newswise A particular molecular pathway permits stem cells in pediatric bone cancers to grow rapidly and aggressively, according to researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center.

In normal cell growth, the Hippo pathway, which controls organ size in animals, works as a dam, regulating cell proliferation. What the researchers found is that the transcription factor of a DNA binding protein called sex determining region Y box 2, or Sox2 for short, which normally maintains cell self-renewal, actually releases the floodgates in the Hippo pathway in osteosarcomas and other cancers, permitting the growth of highly aggressive, tumor-forming stem cells.

Results from the study are to be published in the journal Nature Communications online April 2.

This study is one of the first to identify the mechanisms that underlie how an osteosarcoma cancer stem cell maintains its tumor-initiating properties, says senior study investigator Claudio Basilico, MD, the Jan T. Vilcek Professor of Molecular Pathogenesis at NYU Langone and a member of its Perlmutter Cancer Center.

In the study, the investigators used human and mouse osteosarcomas to pinpoint the molecular mechanisms that inhibit the tumor-suppressive Hippo pathway. The researchers concluded that Sox2 represses the functioning of the Hippo pathway, which, in turn, leads to an increase of the potent growth stimulator Yes Associated Protein, known as YAP, permitting cancer cell proliferation.

Our research is an important step forward in developing novel targeted therapies for these highly aggressive cancers, says study co-investigator Alka Mansukhani, PhD, an associate professor at NYU Langone and also a member of the Perlmutter Cancer Center. One possibility is to develop a small molecule that could knock out the Sox2 transcription factor and free the Hippo pathway to re-exert tumor suppression.

Mansukhani adds that the research suggests that drugs such as verteporfin, which interfere with cancer-promoting YAP function, might prove useful in Sox2-dependent tumors.

The study expands on previous work in Basilicos and Mansukhanis molecular oncology laboratories at NYU Langone and on earlier work by Upal Basu Roy, PhD, MPH, the lead study investigator, who found that Sox2 was an essential transcription factor for the maintenance of osteosarcoma stem cells.

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Key Mechanism Identified in Pediatric Bone Cancers That Allows Proliferation of Tumor-Forming Stem Cells

Researchers produce iPSC model to better understand genetic lung/liver disease

By Stem Cell Medical Center

(Boston)--Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

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Funding was provided by an ARRA stimulus grant (1RC2HL101535-01) awarded by the National Institutes of Health (NIH) to Boston University School of Medicine, Boston Medical Center and the Children's Hospital of Philadelphia. Additional funding was provided by K08 HL103771, FAMRI 062572_YCSA, an Alpha-1 Foundation Research Grant and a Boston University Department of Medicine Career Investment Award. Additional grants from NIH 1R01HL095993 and 1R01HL108678 and an ARC award from the Evans Center for Interdisciplinary Research at Boston University supported this work.

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Researchers produce iPSC model to better understand genetic lung/liver disease

'Open' stem cell chromosomes reveal new possibilities for diabetes

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Researchers map chromosomal changes that must take place before stem cells can be used to produce pancreatic and liver cells

IMAGE:These are pancreatic cells derived from embryonic stem cells. view more

Credit: UC San Diego School of Medicine

Stem cells hold great promise for treating a number of diseases, in part because they have the unique ability to differentiate, specializing into any one of the hundreds of cell types that comprise the human body. Harnessing this potential, though, is difficult. In some cases, it takes up to seven carefully orchestrated steps of adding certain growth factors at specific times to coax stem cells into the desired cell type. Even then, cells of the intestine, liver and pancreas are notoriously difficult to produce from stem cells. Writing in Cell Stem Cell April 2, researchers at University of California, San Diego School of Medicine have discovered why.

It turns out that the chromosomes in laboratory stem cells open slowly over time, in the same sequence that occurs during embryonic development. It isn't until certain chromosomal regions have acquired the "open" state that they are able to respond to added growth factors and become liver or pancreatic cells. This new understanding, say researchers, will help spur advancements in stem cell research and the development of new cell therapies for diseases of the liver and pancreas, such as type 1 diabetes.

"Our ability to generate liver and pancreatic cells from stem cells has fallen behind the advances we've made for other cell types," said Maike Sander, MD, professor of pediatrics and cellular and molecular medicine and director of the Pediatric Diabetes Research Center at UC San Diego. "So we haven't yet been able to do things like test new drugs on stem cell-derived liver and pancreatic cells. What we have learned is that if we want to make specific cells from stem cells, we need ways to predict how those cells and their chromosomes will respond to the growth factors."

Sander led the study, together with co-senior author Bing Ren, PhD, professor of cellular and molecular medicine at UC San Diego and Ludwig Cancer Research member.

Chromosomes are the structures formed by tightly wound and packed DNA. Humans have 46 chromosomes - 23 inherited from each parent. Sander, Ren and their teams first made maps of chromosomal modifications over time, as embryonic stem cells differentiated through several different developmental intermediates on their way to becoming pancreatic and liver cells. Then, in analyzing these maps, they discovered links between the accessibility (openness) of certain regions of the chromosome and what they call developmental competence - the ability of the cell to respond to triggers like added growth factors.

"We're also finding that these chromosomal regions that need to open before a stem cell can fully differentiate are linked to regions where there are variations in certain disease states," Sander says.

In other words, if a person were to inherit a genetic variation in one of these chromosomal regions and his or her chromosome didn't open up at exactly the right time, he or she could hypothetically be more susceptible to a disease affecting that cell type. Sander's team is now working to further investigate what role, if any, these chromosomal regions and their variations play in diabetes.

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'Open' stem cell chromosomes reveal new possibilities for diabetes

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