Stem Cells Help Kidney-Transplant Patients Skip Rejection Drugs in Study

By Michelle Fay Cortez - Wed Mar 07 19:16:55 GMT 2012

Kidney transplant patients given a mixture of stem cells from their organ donor were able to quit taking anti-rejection medicine in a small study, suggesting that life-long reliance on the toxic drugs may be avoidable.

Five of eight patients treated were able to stop taking about a dozen pills a day to suppress their immune systems. The drugs, which prevent rejection and stop tissue from a donated kidney from attacking the patient, can damage the transplant and cause diabetes, infections, heart disease and cancer.

The breakthrough, reported in the journal Science Translational Medicine, mixed stem cells from the donors infection-fighting immune system with the patients natural immune system. The result enabled tissue from both to co-exist in the transplant patient without either being seen as foreign by the immune system, researchers said.

The results may potentially have an enormous, paradigm- shifting impact on solid-organ transplantation, wrote James Markmann and Tatsuo Kawai from Massachusetts General Hospital in Boston, in an editorial accompanying the study. Although only a taste of things to come, few transplant developments in the past half-century have been more enticing than these that put transplantation tolerance within our grasp.

The findings are particularly striking since the patients werent perfect tissue matches with the living donors. The mismatch traditionally makes it more difficult for the donated organ to survive since the patients immune system perceives the unfamiliar tissue as a threat.

Its been a longstanding goal in transplantation to achieve tolerance, to get the recipient to see the donor organ as part of itself, said Joseph Leventhal, a surgeon at Northwestern Memorial Hospital in Chicago and the lead author. A road to tolerance now exists, he said.

Having two immune systems blend into one is called a chimerism. The long-lasting effect seen in the study may stem from the manipulation of stem cells taken from the donor in advance of the surgery, according to the report.

The cells were sent to Suzanne Ildstad, director of the Institute of Cellular Therapeutics at the University of Louisville in Kentucky. There facilitating cells that help transplants take hold were identified and used to enrich the mixture, which was given to the patient the day after surgery.

The researchers didnt provide details on how they crafted the stem cell mix, which may make it difficult for other investigators to confirm the findings, Markmann and Kawai wrote.

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Stem Cells Help Kidney-Transplant Patients Skip Rejection Drugs in Study

UGA study reveals basic molecular 'wiring' of stem cells

Public release date: 1-Mar-2012 [ | E-mail | Share ]

Contact: Stephen Dalton sdalton@uga.edu 706-542-9857 University of Georgia

Athens, Ga. Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell hasuntil noweluded scientists.

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We'll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton's study, on the other hand, reveals that a complex interplay of several molecules controls the "switch" that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell researchfiguring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an "off" position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton's team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

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UGA study reveals basic molecular 'wiring' of stem cells

A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

Embryonic stem cells hold great potential for the development of cellular therapies, where stem cells are used to repair tissue damaged by disease or trauma. This is due to their unique ability to renew themselves and differentiate into any specific types of cell in the body. One of the challenges with cellular therapies is ensuring that ESCs are fully and efficiently differentiated into the correct cell type. This study sheds light on understanding how ESCs are regulated, which is essential to overcome these challenges and turn the vision of cell therapies into reality.

Using a mouse model, the team of scientists from IMB showed that high levels of Amd1 , a key enzyme in the polyamine synthesis pathway, is essential for maintenance of the ESC state and self renewal of ESCs. To further demonstrate the critical role of Amd1 in ESC self-renewal, the scientists showed that increasing Amd1 levels led to delayed ESC differentiation. The research also revealed that downregulation of Amd1 was necessary for differentiation of ESCs into neural precursor cells and that Amd1 is translationally regulated by a micro-RNA (miRNA), the first ever demonstration of miRNA-mediated regulation of the polyamine pathway.

While the polyamine pathway is well established and polyamines are known to be important in cancer and cell proliferation, their role in ESC regulation until now was unknown. This novel discovery, linking polyamine regulation to ESC biology, came about when the team set up a genome-wide screen to look for mRNAs under translational control in order to identify new regulators of ESC differentiation to neural precursor cells.

Dr Leah Vardy, Principle Investigator at the IMB and lead author of the paper, said, "The polyamines that Amd1 regulate have the potential to regulate many different aspects of self renewal and differentiation. The next step is to understand in more detail the molecular targets of these polyamines both in embryonic stem cells and cells differentiating to different cellular lineages. It is possible that manipulation of polyamine levels in embryonic stem cells through inhibitors or activators of the pathway could help direct the differentiation of embryonic stem cells to more clinically useful cell types."

Prof. Birgitte Lane, Executive Director of IMB, said, "This is a fine piece of fundamental research that will have breakthrough consequences in many areas and can bring about far-reaching applications. Developing cellular therapies is just one long-term clinical benefit of understanding ESC biology, which can also help develop stem cell systems for disease modeling, developing new drugs as well as a tool for researchers to answer other biological questions."

Notes for editors: The research findings can be found in the 1st March issue of Genes and Development under the title, "AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells" by Dawei Zhang (1,4), Tianyun Zhao (1,4), Haw Siang Ang (2), Peini Chong (1), Ryotaro Saiki (3), Kazuei Igarashi (3), Henry Yang (2), and Leah A. Vardy (1,5).

1. Institute of Medical Biology, A*STAR, Singapore 2. Cancer Science Institute, National University of Singapore 3. Graduate School of Pharmaceutical Sciences, Chiba University, Japan 4. These authors contributed equally to this work 5. Corresponding author

About the Institute of Medical Biology (IMB)

IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, the 7th and youngest of the BMRC Research Institutes, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life.

IMB hosts 20 research teams of international excellence in stem cells, genetic diseases, cancer and skin and epithelial biology, and works closely with clinical collaborators to target the challenging interface between basic science and clinical medicine. Its growing portfolio of strategic research topics is targeted at translational research on the mechanisms of human diseases, with a cell-to-tissue emphasis that can help identify new therapeutic strategies for disease amelioration, cure and eradication.

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A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

Stem cell fertility treatments could be risky for older women

Harvard scientists are challenging traditional medical logic that dictates that women are born with a finite amount of eggs.  The scientists said they have discovered the ovaries of young women harbor rare stem cells that are in fact capable of producing new eggs.

If properly harnessed, those stem cells may someday lead to new treatments for women suffering from infertility due to cancer or other diseases – or for those who are simply getting older, according to the researchers.  Lead researcher Jonathan Tilly of Harvard's Massachusetts General Hospital has co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.

The idea that women are born with all the egg cells – called oocytes – they’ll ever have has been called into question by past research, which found egg-producing stem cells in adult mice.

In this latest study, Harvard researchers, in collaboration with Japanese scientists, used donated frozen ovaries from 20 year olds and ‘fished out’ the purported stem cells.  

The researchers inserted a gene into the stem cells, which caused them to glow green.  If the cells produced eggs, those would glow green, too.

The researchers first watched through a microscope as new eggs grew in a lab dish.  They then implanted the human tissue under the skin of mice to provide a nourishing blood supply.  Within two weeks, they observed green-tinged cells forming.

While the work of the Harvard scientists does show potential, there are still questions as to whether the cells are capable of growing into mature, usable eggs.

If so, researchers said, it might be possible one day to use the stem cells in order to grow eggs in lab dishes to help preserve cancer patients’ fertility, which can be harmed by chemotherapy.

Now, I just want to say, while this would be a remarkable discovery – if it pans out – I do have a few concerns. 

I think for specific patients in prime, childbearing ages, who are at risk of losing their fertility for one reason or another, this could be a fruitful discovery for them.

Be that as it may, I am totally against commercializing this technology to the point where women going through menopause look at this as another way of getting pregnant.  For many, this could create incredibly high-risk pregnancies, among other medical problems.

While science is capable of great discovery and innovation – particularly in the field of stem cells – I believe that with reproductive medicine, we should move forward with great caution to minimize any risk to mother and baby.

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Stem cell fertility treatments could be risky for older women

Stem cell find offers hope for infertility

Stem cell find offers hope for infertility

By Lauran Neergard

Monday, February 27, 2012

An experiment that produced human eggs from stem cells could one day be a boon for women who are desperate to have a baby, according to a study published yesterday.

The work sweeps away the belief that a woman has only a limited stock of eggs and replaces it with the theory that the supply is continuously replenished from precursor cells in the ovary, its authors said.

If the report is confirmed, harnessing those stem cells might one day lead to better treatments for women left infertile because of disease — or simply because they’re getting older.

"Our current views of ovarian aging are incomplete. There’s much more to the story than simply the trickling away of a fixed pool of eggs," said lead researcher Jonathan Tilly of Harvard’s Massachusetts General Hospital, who had long hunted these cells in a series of studies.

His previous work drew fierce scepticism. Independent experts urged caution about the latest findings.

A key next step is to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University’s Feinberg School of Medicine.

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs were born and matured.

"This is going to spark renewed interest, and more than anything else it’s giving us some new directions to work in," David Albertini, director of the University of Kansas’ Center for Reproductive Sciences said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age.

Tilly first challenged that notion in 2004, reporting the ovaries of adult mice harbour some egg-producing stem cells.

He collaborated with scientists in Japan, who were freezing ovaries donated by healthy 20-somethings. Tilly also had to address a criticism: How to tell if he was finding true stem cells or just very immature eggs.

His team latched onto a protein believed to sit on the surface of only those purported stem cells and fished them out. To track what happened next, they inserted a gene that makes some jellyfish glow green into those cells. If the cells made eggs, those would glow, too. "Bang, it worked — cells popped right out," said Tilly.

a d v e r t i s e m e n t

This appeared in the printed version of the Irish Examiner Monday, February 27, 2012

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Stem cell find offers hope for infertility

Stem Cells China-Switzerland.wmv – Video

11-08-2011 07:03 Banking of Stem Cells in Switzerland with Med Cell Europe AG. Your best investment for a healthy future.

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Stem Cell Treatment for T-6 Spinal Cord Injury – Video

20-09-2011 17:12 After suffering a T-6 spinal cord injury, Tim Bishop underwent two stem cell treatments at the Stem Cell Institute in Panama City, Panama. Watch him demonstrate the remarkable gains he's made thus far. He also discusses his transformation from the despair of being bedridden and just "arms and a head" to the hope of one day walking again. "This is reality!"

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Stem Cell Treatment for T-6 Spinal Cord Injury - Video

Adult Stem Cell Success Stories – Barry Goudy – Video

03-02-2012 15:53 When Barry Goudy found out he had multiple sclerosis he feared the worst. Doctors told him he might lose his eye sight and the ability to walk. As a very active husband, father and hockey coach, Barry couldn't think of anything worse than losing his ability to get around. But then he learned of a new way to treat MS with a stem cell transplant. The transplant worked and today he's living proof of the miracles that can come from Adult Stem Cell Research.

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Adult Stem Cell Success Stories - Barry Goudy - Video

ImmunoCellular Therapeutics To Present at Targeting Stem Cells Symposium during 19th Annual Molecular Medicine Tri …

LOS ANGELES--(BUSINESS WIRE)--

ImmunoCellular Therapeutics, Ltd. (“ImmunoCellular” or the “Company”) (OTCBB: IMUC –News), a biotechnology company focused on the development of novel immune-based cancer therapies, today announced that John Yu, MD, Chairman and Chief Scientific Officer of ImmunoCellular Therapeutics, will deliver a presentation at the Cambridge Healthtech Institute’s inaugural Targeting Stem Cells Symposium as a part of the 19th Annual Molecular Medicine Tri-Conference from February 19-23, 2012. Dr. Yu will present during a session highlighting Emerging Cancer Stem Cell Therapeutics, featuring the Company’s discovery and development of cancer stem cell therapy.

The Cambridge Healthtech Institute’s Targeting Cancer Stem Cells Symposium reflects a growing interest in cancer stem cells and their developing importance in the field of oncology, as more pharmaceutical and biotech companies have begun to focus on cancer stem cells as oncological drug targets. The symposium will feature case studies from those working with cancer stem cells, a history of the role of cancer stem cells in treatment resistance, as well as highlights from ongoing novel cancer stem cell therapeutic development programs and platforms.

About ImmunoCellular Therapeutics, Ltd.

IMUC is a Los Angeles-based clinical-stage company that is developing immune-based therapies for the treatment of brain and other cancers. The Company recently commenced a Phase II trial of its lead product candidate, ICT-107, a dendritic cell-based vaccine targeting multiple tumor associated antigens including those associated with cancer stem cells for glioblastoma treatment. To learn more about IMUC, please visit www.imuc.com.

Forward-Looking Statements

This press release contains certain forward-looking statements that are subject to a number of risks and uncertainties, including the risk that any patents issued covering IMUC’s vaccine technology will not provide significant commercial protection for IMUC’s technology or products; the risk that the safety and efficacy results obtained in the Phase I trial for the dendritic cell- based vaccine will not be confirmed in subsequent trials; the risk that the correlation between immunological response and progression-free and overall survival in the Phase I trial for ICT-107 will not be reflected in statistically significant larger patient populations; the risk that IMUC will not be able to secure a partner company for development or commercialization of ICT-107. Additional risks and uncertainties are described in IMUC's most recently filed SEC documents, such as its most recent annual report on Form 10-K, all quarterly reports on Form 10-Q and any current reports on Form 8-K. IMUC undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

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ImmunoCellular Therapeutics To Present at Targeting Stem Cells Symposium during 19th Annual Molecular Medicine Tri ...

Stem cell injection successfully treats urinary incontinence

It started when Deborah Bishop was still in her 20s.

Always athletic -- she had participated in field hockey, speed skating and baseball -- Ms. Bishop was doing jumping jacks when she noticed to her embarrassment that she had leaked urine.

As the weeks wore on, the Canadian woman began to have more and more of these accidents. It wasn't just strenuous exercise that caused them, but also being tickled or coughing or sneezing.

The condition is known as stress urinary incontinence, and researchers say it may affect hundreds of millions of people around the world, primarily women, who are more susceptible because of their anatomy.

Today, Ms. Bishop, 54, is "90 percent" normal on her urinary leakage, she said -- all because of an injection of her own stem cells that she received three years ago.

The cells, known officially as autologous muscle-derived cells, were taken out of her thigh, multiplied several times over in the lab, and then injected into the muscles around her urethra, the opening at the neck of the bladder.

While many people still associate the phrase "stem cells" with ethical debates over using embryos, these stem cells have nothing to do with that.

All of us have stem cells in various parts of our bodies that can develop into mature cells and are used to repair muscle, nerve and tissue damage.

In this case, researcher Johnny Huard at the University of Pittsburgh developed a technique for finding stem cells in muscle tissue and then purifying and multiplying them. The biomedical firm Cook MyoSite Inc. bought the licensing rights to his technique and is overseeing the current tests on treating stress urinary incontinence.

The idea is that the stem cells will create new cells that will strengthen the muscles that control urination. Even though the initial trials were focused on testing the safety of the procedure, 60 to 70 percent of the women have shown a significant decrease in their urinary leakage, said Ryan Pruchnic, Cook MyoSite's director of operations.

Lesley Carr, Ms. Bishop's physician and a urologist at Sunnybrook Health Sciences Centre in Toronto, said there is no medication that helps with this most prevalent form of incontinence. Up to now, the primary last-resort therapy has been surgical insertion of a mesh sling around the urethra.

The surgery is effective, Dr. Carr said, but "there are rare but recognized complications," including pain and infections, and women face up to six weeks of restricted activity after the operation.

That was a big obstacle for Ms. Bishop, not only because she is so physically active, but because she was in the middle of a house renovation when she sought help for her condition.

"I told Dr. Carr I couldn't afford to be out of commission for six weeks," she recalled, "and that's when she must have mentioned the stem cell trial to me."

In July 2009, she had a piece of her outer thigh muscle removed under local anesthesia, a procedure she admits left her feeling "like I'd been kicked by a horse" for about a week.

Researchers then located and multiplied the stem cells in her muscle tissue, and the following September, she had them injected into the muscles around her urethra. The entire injection took about five minutes, she said, and she felt nothing.

The improvement was gradual after that. "I noticed a difference in a couple months," she said, "and a significant difference in four or five months. I thought what made it really unique was that it was using my own muscle cells."

The procedure means that today, she can do her strenuous morning exercises of standing broad jumps and stride jumps without having to wear heavy pads to absorb leakage.

The latest trials with the stem cells are the first to enroll women who will either get real stem cells or placebo injections. Cook MyoSite hopes to have solid results and be able to bring the procedure to market by 2015, Mr. Pruchnic said.

The company has also begun initial tests of the muscle stem cells in people who have had heart attacks or are experiencing chronic heart failure, in hopes they will restore the strength and flexibility of cardiac muscle.

By using a person's own cells, Dr. Carr noted, there is no need for patients to take immunosuppressive medications. She believes such regenerative medicine "will be the wave of the future in most fields" of health care.

Ms. Bishop is certainly sold.

"I've got a girlfriend who's had three children and is very physically active, and she's struggling with stress incontinence now, and so I'm an advocate for this.

"It was an excellent experience for me, and I would highly recommend it to anyone."

Mark Roth: mroth@post-gazette.com or 412-263-1130.

First published on February 13, 2012 at 12:00 am

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Stem cell injection successfully treats urinary incontinence