Category Archives: Cell Medicine

ST. LOUIS -

Sickle cell is a serious disease that causes pain, anemia, infection, organ damage and even stroke. Its the most common inherited blood disorder in the United States.

The good news is bone marrow transplants can be a cure. The bad news is not every patient has a matching donor. Now, researchers are looking at a new way to offer more patients transplants.

Madisyn Travis is like any other 9-year-old, but theres something that sets Madisyn apart. She has sickle cell, an inherited red blood cell disease.

"It makes me feel bad, and sometimes I have to go to the hospital," Madisyn said.

"It's really hard to see her life interrupted," said Denise Travis, Madisyn's mom.

Soon, however, Madisyn will get a bone marrow transplant to cure her disease. Her little brother or sister are both matches, and one will be the donor.

Madisyn is one of the lucky ones. Only 14 percent of patients have a matching sibling.

"Ten years ago, we'd just tell them, 'Sorry, you have no family member. We cant transplant you,'" said Dr. Shalini Shenoy, professor of pediatrics and medical director, pediatric stem cell transplant program, Washington University School of Medicine, St. Louis Children's Hospital.

Shenoy is studying a new option for patients without related donors. Stem cells from a baby's umbilical cord can be infused in the arm. They travel to the bone marrow, settle there and make new cells.

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Health Beat: Stem cells to cure sickle cell

PUBLIC RELEASE DATE:

8-Jan-2014

Contact: David McKeon DMckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (January 8, 2014) Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) successfully generated a stem cell model of familial Alzheimer's disease (FAD). Using this stem cell model, researchers identified fourteen genes that may be implicated in the disease and one gene in particular that shows the importance that inflammation may play in the brain of Alzheimer's patients.

In this study, published today in PLOS ONE, the team of scientists produced stem cells and neural precursor cells (NPCs), representing early neural progenitor cells that build the brain, from patients with severe early-onset AD with mutations in the Presenilin 1 (PSEN1) gene. These NPCs had elevated Abeta42/Abeta40 ratios, indicating elevation of the form of amyloid found in the brains of Alzheimer's patients. These levels were greater than those in adult cells that did not have the PSEN1mutation. This elevated ratio showed that these NPCs grown in the petri dish were accurately reflecting the cells in the brains of FAD patients.

"Our ability to accurately recapitulate the disease in the petri dish is an important advance for this disease. These genes provide us with new targets to help elucidate the cause of sporadic forms of the disease as well provide targets for the discovery of new drugs," said Susan L. Solomon, Chief Executive Officer of The New York Stem Cell Foundation.

"The gene expression profile from Noggle's familial Alzheimer's stem cells points to inflammation which is especially exciting because we would not usually associate inflammation with this particular Alzheimer's gene. The greatest breakthroughs come with 'unknown unknowns', that is, things that we don't know now and that we would never discover through standard logic," said Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at the Icahn School of Medicine at Mount Sinai and a co-author on the study. Gandy is also Associate Director of the NIH-Designated Mount Sinai Alzheimer's Disease Research Center.

The researchers generated induced pluripotent stem (iPS) cells from affected and unaffected individuals from two families carrying PSEN1 mutations. After thorough characterization of the NPCs through gene expression profiling and other methods, they identified fourteen genes that behaved differently in PSEN1 NPCs relative to NPCs from individuals without the mutation. Five of these targets also showed differential expression in late onset Alzheimer's disease patients' brains. Therefore, in the PSEN1 iPS cell model, the researchers reconstituted an essential feature in the molecular development of familial Alzheimer's disease.

Although the majority of Alzheimer's disease cases are late onset and likely result from a mixture of genetic predisposition and environmental factors, there are genetic forms of the disease that affect patients at much earlier ages. PSEN1 mutations cause the most common form of inherited familial Alzheimer's disease and are one hundred percent penetrant, resulting in all individuals with this mutation getting the disease.

The identification of genes that behaved differently in patients with the mutation provides new targets to further study and better understand their effects on the development of Alzheimer's disease. One of these genes, NLRP2, is traditionally thought of as an inflammatory gene.

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Stem cell research identifies new gene targets in patients with Alzheimer's disease

New York, NY (PRWEB) January 08, 2014

A stem cell model of familial Alzheimers disease (FAD) was successfully generated, allowing researchers to identify 14 genes potentially implicated in the disease. One gene in particular demonstrates the important role inflammation may play in the brain of Alzheimers patients. The study was completed by scientists at The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) and funded in part by the Cure Alzheimers Fund(CAF).

In the study published today in PLOS ONE, a team of scientists produced stem cells and neural precursor cells (NPCs), representing early neural progenitor cells that build the brain from patients with severe early-onset AD with mutations in the Presenilin 1 (PSEN1) gene. These NPCs had elevated Abeta42/Abeta40 ratios, indicating elevation of the form of amyloid found in the brains of Alzheimers patients. These levels were greater than those in adult cells that did not have the PSEN1 mutation. This elevated ratio shows that the NPCs grown in the petri dish accurately reflected the cells in the brains of FAD patients.

"The gene expression profile from the familial Alzheimers stem cells points to inflammation, which is especially exciting because we would not usually associate inflammation with this particular Alzheimer's gene," said Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at the Icahn School of Medicine at Mount Sinai and a co-author on the study. Gandy is also Associate Director of the NIH-Designated Mount Sinai Alzheimers Disease Research Center and leader of the Cure Alzheimers Fund Stem Cell Consortium.

"This is the kind of innovative science that will help us better understand the cause of Alzheimers and how to approach the disease with effective therapies," said Tim Armour, President and CEO of Cure Alzheimers Fund (CAF). "It also showcases how targeted investment of critical resources can make a difference in finding solutions to this debilitating disease."

The researchers generated induced pluripotent stem (iPS) cells from affected and unaffected individuals from two families carrying PSEN1 mutations. After thorough characterization of the NPCs through gene expression profiling and other methods, they identified 14 genes that behaved differently in PSEN1 NPCs relative to NPCs from individuals without the mutation. Five of these targets also showed differential expression in late onset Alzheimers disease patients brains. Therefore, in the PSEN1 iPS cell model, the researchers reconstituted an essential feature in the molecular development of familial Alzheimers disease.

The studys co-lead authors Sam Gandy, MD, PhD and Scott Noggle, PhD are both members of CAFs Stem Cell Consortium, which supported this research. The Stem Cell Consortium is an international group of scientists collaborating on innovative research that investigates, for the first time, the brain cells from individuals with the common form of Alzheimers disease. Other members of the Consortium include Kevin Eggan, PhD, of Harvard University, Marc Tessier-Lavigne, PhD, of Rockefeller University, Doo Kim, PhD, of Harvard Medical School, and Tamir Ben-Hur, MD, PhD, of Hadassah University.

Stem cells are the least mature cells in the body. This means they can be treated with a defined cocktail of factors that can cause maturation of cells along discrete cell types. With iPS cells, which are cells that can become any cell type in the body, it now is possible to take skin cells from adults and return them to an immature state. By redirecting skin cells from Alzheimers patients and turning them into nerve cells, investigators are able to study adult Alzheimers neurons (nerve cells) in the lab.

Although the majority of Alzheimers disease cases are late onset and likely result from a mixture of genetic predisposition and environmental factors, there are genetic forms of the disease that affect patients at much earlier ages. PSEN1 mutations cause the most common form of inherited familial Alzheimers disease and are one hundred percent penetrant, resulting in all individuals with this mutation getting the disease.

Identifying genes that behaved differently in patients with the mutation provides new targets to further study and better understand their effects on the development of Alzheimers disease. One of these genes, NLRP2, is traditionally thought of as an inflammatory gene.

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Breakthrough Research Provides Valuable Insight On Cause Of Alzheimer’s

Cofounder of Stem Cell Theranostics and StartX Med Divya Nag is attacking one of medicine's biggest problems: the fact that most types of human cellslike those in the heart or liverdie when you keep them in a petri dish. This makes testing new drugs a risky, costly and time-consuming business: 90% of medicines that start clinical trials turn out to be too unsafe or ineffective to market. But a new technology, the induced pluripotent stem cell, may help. Nag's company, Stem Cell Theranostics, was created from technology funded by a $20 million grant from the California Institute of Regenerative Medicine and is closing a venture round. It turns cellsusually from a piece of skininto embryonic-like stem cells, then uses them to create heart cells. These cells can live in petri dishes and be used to test new drugs. Someday they might even replace heart tissue that dies during a heart attack. Three large pharmaceutical companies are customers, though revenues are small. Nag, who was already publishing in prestigious scientific journals when she was an undergraduate, dropped out of Stanford to pursue her dream. No regrets: "Our technology was so promising and I was so passionate about it that nothing else made sense to me," she says. "It was very clear this was what I wanted to do."

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2014 30 Under 30: Science & Healthcare

Stanford has received a vast sum of money to study a tiny population of deadly cancer cells, a gift that could help combat the heartbreak of phoenixlike disease recurrence.

The $90 million from the New York City-based Ludwig Fund will boost research at the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford's School of Medicine, where scientists are studying cancer stem cells for ways to tear out the roots of tumors.

Stanford is one of six institutions to share in Ludwig's $540 million contribution to the field of cancer research, announced Monday. Endowed by the late billionaire Daniel K. Ludwig, a self-made American shipping and real estate magnate who died in 1992, the fund supports cancer research that might be otherwise dependent on the whims of government or corporate support.

"This extraordinary gift will spur innovation well into the future," said Stanford president John Hennessy, calling it "a tremendous vote of confidence."

Billions of dollars have been spent on cancer research since President Richard M. Nixon declared war on the disease in 1971. Yet the fight is going slower than most had hoped, with small changes in the death rate over the decades since.

Part of the problem, scientists think, it that some cancers are driven by hidden cancer stem cells -- which remain tenacious even after treatment, reasserting themselves and continuing to grow. Their discovery by Canadian scientist John Dick in 1994 profoundly altered our concept of cancer biology.

If such cells are proven to be the determinant of relapse, the implication for cancer therapy is enormous. Any treatment that leaves behind residual cancer stem cells would inevitably lead to a relapse.

"These are the subset of cells that self-renew -- they're the dangerous one," said Dr. Irving Weissman, who directs Stanford's Ludwig Center, the only cancer stem cell center of its kind.

Weissman and Dr. Michael Clarke have isolated these cells in many different types of cancers and identified ways they might be vulnerable.

They are hoping to target them through immunotherapy, which enlists key immune system cells to grind up the malignant cells and patrol against their re-emergence.

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Stanford gets $90 million cancer study grant

January 3, 2014

Rebekah Eliason for redOrbit.com Your Universe Online

Early reports indicate that lay opinions regarding stem cell research with stem cells made from skin or other tissues, known as induced pluripotent stem cells (iPSCs), are generally positive, despite several ethical concerns.

Regardless of personal benefit, most patients indicated during focus group discussions that they would be will to participate in iPSC. When considering donating tissue, patients raised concern regarding consent, privacy and transparency. Jeremy Sugarman, senior author and the Harvey M. Meyerhoff Professor of Bioethics and Medicine at the John Hopkins Berman Institute of Bioethics, said, Bioethicists, as well as stem cell researchers and policy-makers, have discussed the ethical issues of induced pluripotent stem cells at length, but we didnt have any systematic information about what patients think about these issues, and that is a huge part of the equation if the potential of this research is to be fully realized.

Somewhat taking the edge off of the controversy is the fact that iPSCs do not require the destruction of a human embryo. Using iPSCs in research is extremely valuable in the development of new drugs, disease study and may help develop medical treatments. Although still far off, Sugarman explained that there is hope that iPSCs could eventually be used in the development of organs for transplantation that the bodys immune system will not attack since they can be formed from the persons own cells.

In all five of the focus groups, consent for iPSC research by the patient was highly important. Several of the patients believed that properly informed consent could alleviate other concerns about privacy, the immortalization of cells, and the commercialization of stem cells.

The report noted a strong desire among participants to have full disclosure of the anticipated uses. Some of the participants expressed a desire to be able to veto some of the uses of their cells. Although the authors recognize the practical difficulties of this request, they hope their study will help to prompt investigation into creative approaches to meeting these desires.

The study exposed an additional side to some patients selfless motivations in research participation in relation to eventual commercialization. One participant from the report is quoted as saying, It wont be just taken to become a money maker and the very people who need it the most will no longer be able to benefit from it and another, it was a donation. Its a humanitarian effort.

Unique characteristics of the small study that could influence results were noted by the authors. For example, since the study was conducted in Baltimore, Maryland with patients who have received care at Johns Hopkins, which is home to the first immortal cell line produced from tumor cells that were taken from cancer patient Henrietta Lacks in 1951, related stem cell issues are at the forefront of various focus groups. The report stated, The idea that donated cells would potentially liveforever was unnerving to some participants. In particular, the story about the creation of the HeLa cell line from Henrietta Lacks cervical cancer tissue, taken without consent, was raised in four out of the five focus groups.

In addition, the report suggested that a patients opinion may be affected by their own health and whether they had any personal experience with a debilitating illness. It seems fair to say that everyone experiences serious illness in their lives, whether themselves or through someone they know and care about, and this influences their opinions of healthcare and research, Sugarman says. This study is a first step in getting crucial information about what values are factored into a decision to participate in iPSC research, and what those participants expect from the experience. This study was reported in the journal Stem Cells.

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Public Opinion Generally Supports Stem Cell Research

PUBLIC RELEASE DATE:

2-Jan-2014

Contact: Leah Ramsay lramsay@jhu.edu 202-642-9640 Johns Hopkins Medicine

In an early indication of lay opinions on research with induced pluripotent stem cells (iPSCs), which are stem cells made from skin or other tissues, a new study by bioethicists at Johns Hopkins University indicates that despite some ethical concerns, patients give the research "broad endorsement".

During focus group discussions patients were largely in favor of participating in iPSC research even if personal benefit was unlikely, though they raised concerns about consent, privacy and transparency when considering donating tissue for this research. The bioethicists report their findings in the journal Cell Stem Cell.

"Bioethicists, as well as stem cell researchers and policy-makers, have discussed the ethical issues of induced pluripotent stem cells at length, but we didn't have any systematic information about what patients think about these issues, and that is a huge part of the equation if the potential of this research is to be fully realized," says Jeremy Sugarman, the senior author of the report and the Harvey M. Meyerhoff Professor of Bioethics and Medicine at the Johns Hopkins Berman Institute of Bioethics.

Unlike human embryonic stem cells, iPSCs are derived without destroying a human embryo. Research with human iPSCs is valuable for developing new drugs, studying disease, and perhaps developing medical treatments. Sugarman explains that, while far off, scientists are hopeful that iPSCs could someday be used to develop organs for transplantation that the body's immune system will not attack, because they can be created from the person's own cells.

The study reveals the importance of prior informed consent for those asked to participate in it. According to the report, consent was highly important for patients in all five of the focus groups that were convened. Some patients even suggested that proper informed consent could compensate for other concerns they had about privacy, the "immortalization" of cells, and the commercialization of stem cells.

There was a "strong desire among participants to have full disclosure of the anticipated uses," the report notes, with some participants wanting to be able to veto certain uses of their cells. The authors acknowledge the "practical difficulties" of this request but hope that their findings will "prompt investigation into creative approaches to meeting these desires."

The study also revealed another side to some patients' selfless motivations to participate in research as they might relate to eventual commercialization. The report quotes one participant as saying, "It won't be just taken to become a money maker and the very people who need it the most will no longer be able to benefit from it" and another, "it was a donation. It's a humanitarian effort."

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Study finds patients give 'broad endorsement' to stem cell research

Q: I have been hearing a lot about stem cell injections and was wondering if this would help my painful, arthritic knee?

There is a lot of exciting research and great interest in tissue engineering and regenerative medicine. However, there is also a lot of hype and misinformation out there. Tissue engineering is defined as the application of biological, chemical and engineering principles toward the repair, restoration, or regeneration of living tissues using biomaterials, cells, and factors, alone or in combination.1

The goal of tissue engineering is to regenerate damaged tissue. Tissue Engineering has three primary goals: Harvesting and isolating mesenchymal stem cells (MSCs), providing a scaffold onto which these cells are seeded so that their growth is organized and structured in an effort to duplicate a given tissue that is damaged, and assisting and promoting the growth of these MSCs with growth factors that cause the MSCs to ultimately become the tissue of interest.

There are two types of stem cells: embryonic stem cells, which are derived from fetuses and postnatal stem cells derived from adults. Embryonic stem cells have the ability to proliferate indefinitely in a test tube and the ability to produce all tissue types such as bone, cartilage or muscle. However, in the clinical setting they can cause an immune response in the recipient and can also cause tumors to grow. Furthermore, there are significant ethical concerns with harvesting embryonic stem cells as they are derived from human embryos. Currently in the U.S., the only research that can be performed on embryonic stem cells is that using stem cell lines that were in existence before 2009.

Adult stem cells have the advantage of not having these ethical concerns as they are harvested from the patient. Moreover, there is no immunogenic response as they come from you and also do not cause tumors to develop. However, they do not develop into various tissues as easily as embryonic stem cells do. Adult stem cells can be harvested from a variety of tissues: fat, blood, bone marrow, muscle and other tissue types. The number of stem cells seems to correlate with how much blood flow there is to a given tissue.

MSCs derived from fat or adipose tissue have been primarily used by proponents of regenerative medicine as adipose tissue is easily harvested and has a reasonable concentration of MSCs compared to other sources. Bone cells actually have more potential to differentiate into multiple cell types than fat cells, but harvesting cells from bone is more painful and invasive than harvesting fatty tissue, which most of us would be happy to donate. Anyone who has had a bone marrow biopsy can attest to the pain involved.

Patients who see me in the office with knee pain or knee arthritis often ask me if they would benefit from a stem cell injection. Currently, there is no good evidence in the orthopedic literature to recommend this. Insurance companies do not pay for this procedure, as again, there is no good evidence showing it to be efficacious. Thus, patients have to pay thousands of dollars out of pocket for this procedure. Given the lack of evidence to support it and the cost and possible risks, I do not recommend it. When injecting stem cells harvested from fatty tissue into an arthritic knee for example, these cells are not directed to grow cartilage nor are they directed to grow cartilage in the areas where your knee lacks it. Instead, these stem cells could equally differentiate into fat, bone, scar tissue or cartilage. In turn, you could grown bone on your own remaining cartilage, you could grow scar tissue on your ligaments, etc.

Tissue engineering is an evolving field with many possible exciting applications whose day will come, but unfortunately its clinical applications continue to be quite limited at the current time.

1 Laurencin CT, Ambrosio AM, Borden MD, Cooper JA Jr.: Tissue engineering: Orthopedic applications. Annu Rev Biomed Eng 1999; 1:19-46.

Dr. Rick Cunningham is a Knee and Shoulder Sports Medicine Specialist with Vail-Summit Orthopaedics. He is a Physician for the US Ski Team and Chief of Surgery at Vail Valley Medical Center. Do you have a sports medicine question youd like him to answer in this column? Visit his website at http://www.vailknee.com to submit your topic idea. For more information about Vail-Summit Orthopaedics, visit http://www.vsortho.com.

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Ask a Sports Medicine Doc: Fact and fiction of stem cells

A release from the University of California-Los Angleles written by Shaun Mason reports that researchers at UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered a mechanism by which certain adult stem cells suppress their ability to initiate skin cancer during their dormant phase an understanding that could be exploited for better cancer-prevention strategies. The study, led by Andrew White and William Lowry, was published online Decemeber 15th 2013 in the journal Nature Cell Biology.

The release notes that hfollicle stem cells, the tissue-specific adult stem cells that generate the hair follicles, are also the cells of origin for cutaneous squamous cell carcinoma, a common skin cancer. These stem cells cycle between periods of activation during which they can grow and quiescence (when they remain dormant).

White and Lowry applied known cancer-causing genes to hair follicle stem cells of laboratory mice and found that during the cells dormant phase, they could not initiate skin cancer. Once the cells were in their active period, however, they began growing cancer.

The release quotes White as saying, "We found that this tumor suppression via adult stem cell quiescence was mediated by PTEN, a gene important in regulating the cell's response to signaling pathways. Therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and PTEN must be present for the suppression to work."

The team believes that understanding cancer suppression through quiescence could better inform preventative strategies for certain patients, such as organ transplant recipients, who are particularly susceptible to squamous cell carcinoma, and for those taking the drug vemurafenib for melanoma, another type of skin cancer. The study also may reveal parallels between squamous cell carcinoma and other cancers in which stem cells have a quiescent phase.

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Dormant Adult Stem Cells Suppress Cancer

Los Angeles, Dec 21 : Researchers at UCLA's (University of California, Los Angeles') Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered a mechanism by which certain adult stem cells suppress their ability to initiate skin cancer during their dormant phase an understanding that could be exploited for better cancer-prevention strategies.

The study, which was led by UCLA postdoctoral fellow Andrew White and William Lowry, an associate professor of molecular, cell and developmental biology who holds the Maria Rowena Ross Term Chair in Cell Biology in the UCLA College of Letters and Science, was published online Dec. 15 in the journal Nature Cell Biology.

Hair follicle stem cells, the tissue-specific adult stem cells that generate the hair follicles, are also the cells of origin for cutaneous squamous cell carcinoma, a common skin cancer. These stem cells cycle between periods of activation (during which they can grow) and quiescence (when they remain dormant).

Using mouse models, White and Lowry applied known cancer-causing genes to hair follicle stem cells and found that during their dormant phase, the cells could not be made to initiate skin cancer. Once they were in their active period, however, they began growing cancer.

"We found that this tumor suppression via adult stem cell quiescence was mediated by PTEN, a gene important in regulating the cell's response to signaling pathways," White said.

"Therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and PTEN must be present for the suppression to work."

Understanding cancer suppression through quiescence could better inform preventative strategies for certain patients, such as organ transplant recipients, who are particularly susceptible to squamous cell carcinoma, and for those taking the drug vemurafenib for melanoma, another type of skin cancer.

The study also may reveal parallels between squamous cell carcinoma and other cancers in which stem cells have a quiescent phase.

The research was supported by the California Institute of Regenerative Medicine, the University of California Cancer Research Coordinating Committee and the National Institutes of Health.

--IBNS (Posted on 21-12-2013)

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Adult stem cells suppress cancer while dormant