Stem Cell Clinic

Patient-specific stem cells and personalized gene therapy

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

10-Jul-2014

Contact: Lucky Tran lt2549@cumc.columbia.edu 212-305-3689 Columbia University Medical Center

NEW YORK, NY (July 10, 2014) Columbia University Medical Center (CUMC) researchers have created a way to develop personalized gene therapies for patients with retinitis pigmentosa (RP), a leading cause of vision loss. The approach, the first of its kind, takes advantage of induced pluripotent stem (iPS) cell technology to transform skin cells into retinal cells, which are then used as a patient-specific model for disease study and preclinical testing.

Using this approach, researchers led by Stephen H. Tsang, MD, PhD, showed that a form of RP caused by mutations to the gene MFRP (membrane frizzled-related protein) disrupts the protein that gives retinal cells their structural integrity. They also showed that the effects of these mutations can be reversed with gene therapy. The approach could potentially be used to create personalized therapies for other forms of RP, as well as other genetic diseases. The paper was published recently in the online edition of Molecular Therapy, the official journal of the American Society for Gene & Cell Therapy.

"The use of patient-specific cell lines for testing the efficacy of gene therapy to precisely correct a patient's genetic deficiency provides yet another tool for advancing the field of personalized medicine," said Dr. Tsang, the Laszlo Z. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology.

While RP can begin during infancy, the first symptoms typically emerge in early adulthood, starting with night blindness. As the disease progresses, affected individuals lose peripheral vision. In later stages, RP destroys photoreceptors in the macula, which is responsible for fine central vision. RP is estimated to affect at least 75,000 people in the United States and 1.5 million worldwide.

More than 60 different genes have been linked to RP, making it difficult to develop models to study the disease. Animal models, though useful, have significant limitations because of interspecies differences. Researchers also use human retinal cells from eye banks to study RP. As these cells reflect the end stage of the disease process, however, they reveal little about how the disease develops. There are no human tissue culture models of RP, as it would dangerous to harvest retinal cells from patients. Finally, human embryonic stem cells could be useful in RP research, but they are fraught with ethical, legal, and technical issues.

The use of iPS technology offers a way around these limitations and concerns. Researchers can induce the patient's own skin cells to revert to a more basic, embryonic stem celllike state. Such cells are "pluripotent," meaning that they can be transformed into specialized cells of various types.

In the current study, the CUMC team used iPS technology to transform skin cells taken from two RP patientseach with a different MFRP mutationinto retinal cells, creating patient-specific models for studying the disease and testing potential therapies.

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Patient-specific stem cells and personalized gene therapy

Stem cell researcher targets 'seeds' of breast cancer metastasis

By Uncategorized

For breast cancer patients, the era of personalized medicine may be just around the corner, thanks to recent advances by USC Stem Cell researcher Min Yu and scientists at Massachusetts General Hospital and Harvard Medical School.

In a July 11 study in Science, Yu and her colleagues report how they isolated breast cancer cells circulating through the blood streams of six patients. Some of these deadly cancer cells are the "seeds" of metastasis, which travel to and establish secondary tumors in vital organs such as the bone, lungs, liver and brain.

Yu and her colleagues managed to expand this small number of cancer cells in the laboratory over a period of more than six months, enabling the identification of new mutations and the evaluation of drug susceptibility.

If perfected, this technique could eventually allow doctors to do the same: use cancer cells isolated from patients' blood to monitor the progression of their diseases, pre-test drugs and personalize treatment plans accordingly.

In the six estrogen receptor-positive breast cancer patients in the study, the scientists found newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene and fibroblast growth factor receptor gene (FGFR2), among others. They then tested either alone or in combination several anticancer drugs that might target tumor cells with these mutations and identified which ones merit further study. In particular, the drug Ganetspib -- also known as STA-9090 -- appeared to be effective in killing tumor cells with the ESR1 mutation.

"Metastasis is the leading cause of cancer-related death," said Yu, assistant professor in the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC. "By understanding the unique biology of each individual patient's cancer, we can develop targeted drug therapies to slow or even stop their diseases in their tracks."

Story Source:

The above story is based on materials provided by University of Southern California - Health Sciences. The original article was written by Cristy Lytal. Note: Materials may be edited for content and length.

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Stem cell researcher targets 'seeds' of breast cancer metastasis

Is there Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder? – Video

By Uncategorized


Is there Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder?
Dr. Hemangi Sane from Neurogen Brain and Spine Institute show Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder. Published Paper ...

By: Neurogen Brain and Spine Institute

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Is there Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder? - Video

Stem Cells May Ease Urinary Incontinence, Study Says

By Stem Cell Treatment

By Maureen Salamon HealthDay Reporter Latest Womens Health News

FRIDAY, July 11, 2014 (HealthDay News) -- For the millions of women who can't cough, sneeze or laugh without losing bladder control, researchers are testing a treatment that uses stem cells to regenerate weakened urethra muscles.

In a small pilot study, European researchers found that injecting stem cells isolated from patients' own fat tissue improved or eliminated stress incontinence in all participants within a year.

Stress incontinence affects about twice as many women as men because of pelvic floor strain from pregnancy and childbirth.

Most women who choose to treat the condition undergo a procedure that inserts surgical mesh between the urethra and vagina to reduce urine leakage, urologists said. But widening controversy over the use of surgical mesh makes the idea of stem cell treatment even more attractive.

"This is an application that makes sense because of the ease of access to the urethra, which isn't a difficult area to inject," said Dr. Timothy Boone, chairman of urology at Houston Methodist Hospital in Texas, who wasn't involved in the study.

Globally, similar research is under way on the use of stem cells to treat stress incontinence.

However, "a lot of other stem cell therapies are a lot more invasive," Boone added. "It's too soon to tell, but the hope would be that a significant number of women would benefit from this and avoid the possible complications of surgery."

The study is published online in the July issue of the journal Stem Cells Translational Medicine.

Stress incontinence occurs when pelvic floor muscles supporting the bladder and urethra become too weak to prevent urine flow when pressure is placed on the abdomen. The problem can range from being a nuisance to highly debilitating.

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Stem Cells May Ease Urinary Incontinence, Study Says

Injured Argentine winger Angel Di Maria may be resorting to unproven stem cell therapy

By Stem Cell Treatment

Im not betting on it, but if, by some miracle, Argentine winger Angel Di Maria is on the pitch against Germany Sunday in the 2014 World Cup final, get ready for another explosion of interest in stem cell therapy, a now familiar occurrence every time a famous athlete undergoes the treatment.

Di Maria, who either tore or strained a thigh muscle in Argentinas World Cup win over Belgium, is so determined to play in the final that, according to some reports, he is having the muscle injected with stem cells in the hope of healing by Sunday. (This Associated Press report from Thursday said he was practicing at 60 to 80 percent, so Im guessing were talking about a strain.)

If those reports are true, Di Maria will join a long line of elite athletes who have resorted to the unproven and possibly risky therapy. This kind of stem cell therapy is experimental in every sense of the word, according to the International Society for Stem Cell Research. There also is some evidence that the procedure can promote tumor growth or create an immune response to a patients own cells, or that injected stem cells might migrate to another part of the body.

Never mind. There is soccer to be played!

No one denies that stem cells hold promise as a therapy down the road, perhaps in as little as five or 10 years, says Kevin McCormack, communication director for the California Institute for Regenerative Medicine. With $3 billion supplied by voters in a 2004 ballot initiative, the organization is funding trials of the use of stem cell therapies for scarring after heart attacks, sickle cell anemia, leukemia and other conditions.

But for now, stem cells are known to be effective only for certain disorders of the blood, immune system and bone marrow. Beyond that, little has been proven, although clinics in the United States and around the world are offering the therapy and raking in bucks from desperate patients.

Di Maria may even see some benefits, McCormack said. In theory, they might [help] because they may have an anti-inflammatory effect or they may stimulate the bodys own natural healing, he said. But the problem is that they havent done any research to prove that.

The stem cells are harvested from a patients bone marrow and sometimes run through a centrifuge to concentrate them. Then they are injected into the damaged tissue.

For athletes, who are always looking for ways to prolong their careers and bounce back from injury, the fad began in 2010, when Major League pitcher Bartolo Colon had a slurry of stem cells that can turn into a variety of tissues injected into his injured elbow and shoulder. Within months, he was throwing 93 mile per hour fastballs for the New York Yankees. Later, Denver Broncos quarterback Peyton Manning, one of the most famous athletes in the United States, reportedly had stem cell therapy on his injured neck.

McCormack and others express concern that when pro athletes and other celebrities have unproven treatments, it sends the rest of us weekend warriors out in search of the same. Here a good bit of blame goes to us in the media. A 2012 analysis conducted for the journal Molecular Therapyshowed that 72.7 percen of the media coverage of athletes and stem cell therapy didnt address whether the treatment works, and 42 percent referred to alleged benefits. Only 5.7 percent of the stories brought up possible safety issues and risks.

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Injured Argentine winger Angel Di Maria may be resorting to unproven stem cell therapy

No extra mutations in modified stem cells

By Stem Cell Clinic

The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise-the hope of fixing disease-causing genes in humans, for example-as well as questions and safety concerns.

Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells-either for research purposes or to fix a genetic mutation for therapeutic purposes-they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one.

Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world.

He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes-such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro-including gene editing-might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease.

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No extra mutations in modified stem cells

Stem Cell Research in New York State | NYSTEM

By Stem Cell Treatment

(Complete report available in pdf format - 1.6 MB)

Executive Summary I. Introduction II. Methodology and Scope III. The Potential of stem cell research and NYSTEM IV. Findings V. Observations and Recommendations from the NY stem cell research community

Directory of Principal Investigators (available in the PDF above) An updated directory of stem cell scientists in New York State is now available.

This report summarizes data obtained from responses to written surveys and structured personal interviews with stem cell scientists in New York State between June and October, 2007. The findings are accompanied by a directory of the scientists interviewed. The objectives of this initial inquiry were threefold: (i) identify institutions and scientists in New York State with ongoing stem cell research programs; (ii) develop an overview of the scope and directions of these researchers' activities and (iii) solicit the views of the stem cell science community in New York regarding the potential scope and mechanisms of funding by NYSTEM. Letters were sent to 42 institutions that were identified through publicly available funding and publication records as having relevant research efforts. Overall, from 28 responding institutions we received feedback from 162 principal investigators (PI) at 23 institutions in time for inclusion in this report. The first interviews took place July 20 and the most recent visit was October 4; in this span of 10 weeks we interviewed investigators from 21 institutions representing all geographic areas of the state.

Importantly, this inquiry identified a strong community of stem cell scientists across the state, as judged by publications and external funding, with diverse interests and expertise, who are well positioned to take immediate advantage of the opportunities that will be provided by NYSTEM. Within the limits of our surveys and interviews, we estimate that more than 200 scientists head laboratories conducting stem cell related research, and that roughly two-thirds of these have a major focus in some aspect of stem cell science. Our survey demonstrated that 52% of PIs have NIH funding. Based on an examination of public databases in 2006, the research scientists have attracted $39.5 million in National Institutes of Health (NIH) funding for stem cell research, as well as substantial foundation, industry and other types of support for which no comprehensive figures are available. Based on survey responses, their work has resulted in at least 115 patents and 16 licenses. Moreover, we estimate that approximately 1,000 scientists, trainees and support staff are currently employed in their academic and private laboratories conducting stem cell research. The data provide fuel for the need for traineeships. At present, only 58% of PIs have graduate students working on stem cells. The situation is similar but slightly better with postdocs as 67% of PIs report having a postdoc.

Stem cell research in New York is broad in scope and highly collaborative, as about 80% of the investigators reported at least one collaboration. One objective of our inquiry was to ascertain the scope of this research within New York State and determine if there are dominant themes or specific areas of strength. Based on data from 162 scientists, the largest fractions had a focus on cancer, neural disease or aging. Other major topics included hematopoietic and musculoskeletal disease and diabetes. The data also showed that many investigators are engaged in studies of fundamental aspects of stem cell biology. Of the 162 respondents, nearly half reported that their research significantly concerned basic stem cell biology.

The types and sources of stem cells that researchers use in their studies are diverse. The majority of investigators use rodent or other non-human sources to supply stem cells for their research. However, nearly half of the investigators use stem cells of human origin, most of whom employ non-embryonic derived cells of a variety of types: hematopoietic and mesenchymal stem cells from marrow and umbilical cord blood, amniotic stem cells, and organ-specific cells derived from skin, cardiac, liver, kidney and other sources. Also included in this list are cancer stem cells. A smaller but still significant fraction of investigators use human embryonic stem cells (hESCs) in their work, or hold approved protocols and plan to use hESCs in the immediate future. Of 39 investigators, 24 reported using only NIH-approved ("registry") hESC lines and 15 reported using "non-registry" lines. Investigators planning to derive new stem cell lines from embryos deemed non-viable, were included in the "non-registry" hESC group. Several of those involved in hESC work were doing so only through collaborations with investigators at other institutions, and only about half of those using hESCs in their work reported that it represented a large fraction of their effort.

In terms of funding preferences, there was strong, but not universal agreement for the use of an investigator-initiated NIH R01-like grant mechanism that would provide substantial funding to individual laboratories for multiple years. Many also favored an additional mechanism of investigator-initiated funding analogous to the NIH R21 vehicle which encourages higher risk with the promise of greater reward. Many interviewees supported institution-based multi-investigator grants in which several researchers at one institution, or investigators at several institutions, collaborate on complementary aspects of a particular research problem. There was considerable support for individual postdoctoral fellowships or young investigator grants as a mechanism for bringing new talent into the stem cell field. Likewise there was considerable enthusiasm for short -term funding for "sabbaticals" in which investigators could visit another laboratory (inside or outside NYS) to acquire specific training in stem cell science or a field that would benefit particular aspects of stem cell research. In contrast, there was little support for institutional training grants, in which graduate students or postdocs are supported en masse, often to work in assigned labs.

It is clear that the area of hESC research has been constrained by inadequate federal support, and that an important focus of NYSTEM should be to enhance opportunities for hESC studies within appropriate ethical guidelines as established by the Board. Concurrent with this opinion, there was unanimity among these researchers that NYSTEM funding should not be restricted to hESC work, since it is unknown at this time which human stem cell types (embryonic or adult) will be best suited for application to particular diseases. Several investigators involved in translational research noted that there is a major gap in available federal funding for pre-clinical studies that move important findings from animal models to human systems. New York State funding for advanced biotechnology core facilities was identified as important by a number of individuals. In particular, researchers working with non-registry hESC indicated that the duplication of equipment required by current federal funding restrictions was a hardship.

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Stem cell heart failure treatment advances

By Stem Cell Treatment

Stem cells grown under low oxygen. These stem cells from Stemedica are licensed to CardioCell.

CardioCell, a San Diego stem cell company, has started a Phase 2a trial of its treatment for chronic heart failure.

The companys special stem cells will be injected into patients with heart failure not caused by a heart attack. Nearly 2 million Americans have that kind of heart failure.

CardioCell is also testing these stem cells on heart attack patients to help their recovery. The cells are licensed from Stemedica, CardioCell's parent company.

Taken from bone marrow, the stem cells produce chemicals intended to heal malfunctioning heart cells. They are grown under low oxygen conditions, or hypoxia. CardioCell says hypoxia reflects the conditions under which natural stem cells exist. Histogen, also of San Diego, is developing its own kind of low-oxygen stem cells.

Growing stem cells with abundant oxygen reduces their "stemness," and they become prone to differentiate, said Sergey Sikora, CardioCell's president and chief executive.

Sergey Sikora, president and CEO of CardioCell / CardioCell

More than 20 patients are being sought to take part in the study, which is taking place at three locations. These are Emory University in Atlanta, Northwestern University in Chicago, and the University of Pennsylvania in Philadelphia.

Patients will receive injections of the stem cells, and a control group will receive a saline injection. After 90 days, the groups will be reversed. Patients who had received the stem cells will get a saline injection, and the control group will get the stem cells.

The stem cells last for about a month, after which they disappear, Sikora said.

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Stem cell heart failure treatment advances

Lung Institute Reveals New Stem Cell Therapy Case Study

By Stem Cell Treatment

Tampa, FL (PRWEB) July 10, 2014

The Lung Institute works to help people who have received a diagnosis of debilitating lung disease get their quality of life back. The latest case study demonstrates how stem cell therapy can be used effectively to treat interstitial lung disease. After his recent stem cell treatment at the Lung Institute, Al Corter can now complete his daily tasks on his horse farm much faster, and finally attend the Silver Spur Riding Club Open Horse Show the weekend of July 12th in Fonda, NY.

Twelve years ago, Al was exposed to toxic fumes in the workplace and subsequently diagnosed with interstitial lung disease and bronchiectasis, a form of chronic obstructive pulmonary disorder (COPD). Living in upstate New York and running his horse farm, Als serious pulmonary conditions had a major effect on his life. Shortness of breath, coughing, reliance on supplemental oxygen and fatigue were taking a toll. Al needed a new solution.

Al decided to travel to Florida to undergo stem cell treatment at the Lung Institute facility in Tampa. He was seeking an alternative treatment to help with his symptoms. Stem cell therapy is a minimally invasive process that involves extracting stem cells, and then reintroducing them to cue the bodys natural healing processes. The stem cells are taken from the patients own body, so there is no controversy or risk of rejection.

Stem cell therapy is a viable option for many people with lung disease, said Dr. Burton Feinerman, Medical Director of the Lung Institute. Our patients are breathing easier, walking further and depending less on supplemental oxygen.

Prior to stem cell therapy, Al was needing more and more supplemental oxygen. His quality of life had taken a sharp turn downward. Following adipose stem cell treatment, Al is feeling better. He is getting back to the routine at the farm. Al used to use 5 to 6 liters of continuous oxygen to get his outdoor farm work done. Now, he is able to do these daily chores faster, and uses only 4 to 5 liters of oxygen on a pulsing regulator.

Im getting everyday tasks done quicker, said Al. Im using about half the amount of oxygen as I was before to do the same activities. My quality of life has definitely improved.

The Lung Institute has treated hundreds of patients with lung disease from around the country and the world. Regardless of the stage of the disease, patients are able to undergo stem cell therapy, which helps damaged lung tissue, and can lessen their symptoms.

About Lung Institute At the Lung Institute, we are changing the lives of hundreds of people across the nation through the innovative technology of regenerative medicine. We are committed to providing patients a more effective way to address pulmonary conditions and improve quality of life. Our physicians, through their designated practices, have gained worldwide recognition for the successful application of revolutionary minimally invasive stem cell therapies. With over a century of combined medical experience, our doctors have established a patient experience designed with the highest concern for patient safety and quality of care. For more information, visit our website at LungInstitute.com, like us on Facebook, follow us on Twitter or call us today at (855) 469-5864.

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A new genome editing method brings the possibility of gene therapies closer to reality

By Stell Cell Research

PUBLIC RELEASE DATE:

11-Jul-2014

Contact: Jia Liu liujia@genomics.cn BGI Shenzhen

July 3, 2014, Shenzhen, China Researchers from Salk Institute for Biological Studies, BGI, and other institutes for the first time evaluated the safety and reliability of the existing targeted gene correction technologies, and successfully developed a new method, TALEN-HDAdV, which could significantly increased gene-correction efficiency in human induced pluripotent stem cell (hiPSC). This study published online in Cell Stell Cell provides an important theoretical foundation for stem cell-based gene therapy.

The combination of stem cells and targeted genome editing technology provides a powerful tool to model human diseases and develop potential cell replacement therapy. Although the utility of genome editing has been extensively documented, but the impact of these technologies on mutational load at the whole-genome level remains unclear.

In the study, researchers performed whole-genome sequencing to evaluate the mutational load at single-base resolution in individual gene-corrected hiPSC clones in three different disease models, including Hutchinson-Gilford progeria syndrome (HGPS), sickle cell disease (SCD), and Parkinson's disease (PD).

They evaluated the efficiencies of gene-targeting and gene-correction at the haemoglobin gene HBB locus with TALEN, HDAdV, CRISPR/CAS9 nuclease, and found the TALENs, HDAdVs and CRISPR/CAS9 mediated gene-correction methods have a similar efficiency at the gene HBB locus. In addition, the results of deep whole-genome sequencing indicated that TALEN and HDAdV could keep the patient's genome integrated at a maximum level, proving the safety and reliability of these methods.

Through integrating the advantages of TALEN- and HDAdV-mediated genome editing, researchers developed a new TALEN-HDAdV hybrid vector (talHDAdV), which can significantly increase the gene-correction efficiency in hiPSCs. Almost all the genetic mutations at the gene HBB locus can be detected by telHDAdV, which allows this new developed technology can be applied into the gene repair of different kinds of hemoglobin diseases such as SCD and Thalassemia.

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