Biomarkers, Stem Cells Offer New Ways to Treat Deadly Gut Disease in Premature Babies

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Newswise Columbus, OH. Premature babies face a host of medical challenges at birth, but none as deadly and mysterious as a disease called necrotizing enterocolitis (NEC). The condition creates an inexplicable combination of inflammation and infection that causes parts of the intestine to die. NEC progresses at a ruthless speed, leaving physicians with few options typically supportive care, emergency surgery or antibiotics. Only half of newborns who undergo surgery survive, and they often face serious life-long complications.

In the fifty years since necrotizing enterocolitis was first identified, weve accomplished relatively little to change its devastating course. Even worse, we dont know which babies will get it. One minute, a child can appear healthy, but then be dead from NEC hours later, said Gail Besner, MD, chief of pediatric surgery at Nationwide Childrens Hospital.

That may be about to change thanks to two major breakthroughs driven by Besner and Surgeon-in-Chief at Nationwide Childrens R. Lawrence Moss, MD.

After nearly two decades of work, their separate efforts have yielded both the discovery of a biomarker that can help predict which babies will get the disease, as well as treatments that can restore the intestines natural ability to protect itself against NEC.

These researchers advances offer innovative approaches to necrotizing enterocolitis that may someday make it a more predictable and better managed complication of prematurity, said John Barnard, MD, President of the Nationwide Childrens Research Institute and Pediatric Director of The Ohio State University Center for Clinical and Translational Science (CCTS).

Growth factors, stem cells offer gut protection For Besner, the key has always been to prevent NEC before it can start. In the 1990s, she began looking closely at what was happening at the molecular level to an immature bowel in the throes NEC. Besner made a major discovery, observing that a protein called heparin-binding EGF-like growth factor (HB-EGF) which she initially discovered played a life and death role in protecting premature infants from NEC.

In numerous studies, Besner showed that without HB-EGF, the structures within the intestines that maintain barrier function and integrity, including a massive network of nerves and blood vessels, became easily injured and beyond repair. The addition of HB-EGF had the opposite effect, helping protect intestines from injury in animal models of NEC.

From that molecular level understanding of NEC, Besner developed a bigger picture hypothesis about how the nerve damage within an immature gut impacted the diseases development and progression and where a solution might be found.

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Biomarkers, Stem Cells Offer New Ways to Treat Deadly Gut Disease in Premature Babies

Image sensor for analysis of blood samples for early diagnosis of diabetes and Alzheimer's disease

17 hours ago Fig. 1: Semiconductor image sensor

Professor Kazuaki Sawada and Dr. Takigawa of the National Center for Geriatrics and Gerontology and colleagues at Toyohashi University of Technology have established an easy to use, low-cost, rapid, and high sensitivity semiconductor-imaging based medical diagnostic biosensing system for analyzing blood and urine for early diagnosis of ailments including diabetes and Alzheimer's disease.

The new biosensing technology consists of a semiconductor image sensor ( 'charge coupled device' developed by Toyohashi University of Technology) that is sensitive to extremely small changes in electric potential, and microbeads on which antigen-antibody reactions take place. This technology will enable monitoring and diagnosis of diseases for which specific markers are known using very small volumes of blood or urine. Specifically, this technology has detected amiloid beta-peptide, an agent responsible for Alzheimer's disease.

Contracting a disease leads to expression of proteins specific to the diseases in the blood. This new technology is used for early diagnosis of diseases by using this specific protein as the antigen and a marker that captures the protein as the antibody and checking their antigen-antibody reaction. Conventional protocols used to monitor antibody-antigen reactions employ fluorescent probes and detection of fluorescence with microscopic cameras. This process is time consuming because of the necessity to measure fluorescence from the probes and cannot be used to detect low concentrations of antigens when the fluorescence intensity is too low to detect optically.

With this technology, an antigen-antibody reaction is used as in conventional methods, but fluorescence is not measured. Instead, this method employs a semiconductor image sensor to detect minute changes in electric potential generated during an antigen-antibody reaction.

The semiconductor image sensor [Fig. 1] consists of 128 128 pixels that independently sense minute changes in electric potential. The detection sensitivity of antigen-antibody reactions was significantly increased by using microbeads [Fig. 2]. The figures of merit of this technology are given in Table 1. Multiple diseases can also be simultaneously diagnosed by placing different antibodies on different sensing pixels out of a total of 16,384 pixels (128128).

Implementation of the technology will be tested for daily control of lifestyle diseases such as diabetes and in future the technology will be expanded for the early diagnosis of Alzheimer's and Parkinson' diseases.

Explore further: New technique could benefit Alzheimer's diagnosis

More information: Akiteru Kono et al, "Label free bio image sensor for real time monitoring of potassium ion released from hippocampal slices," Sensors and Actuators B 201, 439443, (2014). dx.doi.org/10.1016/j.snb.2014.04.019

A new recombinant antibody can detect and isolate mesenchymal stem cells (MSCs), a nonembryonic source of stem cells with promising applications in tissue engineering, blood stem cell transplantation, and ...

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Image sensor for analysis of blood samples for early diagnosis of diabetes and Alzheimer's disease

Beverly Hills Orthopedic Institute Teams up with Beverly Hills Rejuvenation Center to Offer Comprehensive Anti Aging …

Beverly Hills, California (PRWEB) September 22, 2014

Beverly Hills Orthopedic Institute has now teamed up with the Beverly Hills Rejuvenation Center to offer patients comprehensive anti aging and stem cell therapies. For those individuals desiring to achieve pain relief and avoid the need for joint replacement or cosmetic surgery, treatments at the practices represent the most modern methods available. Call (310) 247-0466 for more information and scheduling.

At Beverly Hills Orthopedic Institute, Dr. Raj offers extensive experience with stem cell procedures for all types of arthritis, sports injuries, fractures, tendonitis and ligament injuries. Frequently, patients are able to delay or avoid the need for joint replacement surgery with the outpatient treatments. Dr. Raj is a Double Board Certified Los Angeles orthopedic doctor who has frequently been named one of LA's Top Orthopedists and also serves as an ABC News medical consultant.

By teaming up with Beverly Hills Rejuvenation Center, the cosmetic aspects of regenerative medicine are included. This includes non surgical facelifts, hair restoration, laser hair removal, photofacials and hormone replacement therapy.

Founded in 2005 by the "wellness experts to the stars Dan Holtz and Devin Haman, Beverly Hills Rejuvenation Center has a well-earned reputation as one of the most comprehensive anti-aging and wellness centers in Los Angeles. Beverly Hills Rejuvenation Center has recently been featured in Malibu magazine, on the Hallmark Channels Home and Family program along with the NBC Nightly News.

Regenerative medicine represents a new paradigm for pain relief and cosmetic procedures. The issues at hand are actually corrected as opposed to simply applying a "band aid." The stem cells offer the capability of restoring and regenerating damaged tissue, whether it be cartilage, skin, muscle or tendons.

For more information and scheduling at either the Beverly Hills Orthopedic Institute or Beverly Hills Rejuvenation Center, call (310) 247-0466.

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New Treatment May Prevent Diabetes After Pancreatitis Surgery

New York, NY (PRWEB) September 22, 2014

Video: Preventing Diabetes After Pancreatectomy - Dr. Beth Schrope

NewYork-Presbyterian/Columbia University Medical Center now offers autologous islet cell transplantation, or auto islet surgery, to prevent diabetes in patients who require a total pancreatectomy. The hospital is the first center in the New York metropolitan area to offer this treatment.

Every year, roughly 87,000 people in the United States receive surgical treatment for pancreatitis, a debilitating condition that causes intense abdominal pain and, potentially, diabetes. Pancreatitis can be so painful that, in some cases, patients must have the entire pancreas removed. While surgery relieves pain in 90 percent of cases, patients are left without the ability to produce insulin, causing a difficult-to-treat form of Type 1 diabetes known as brittle diabetes.

In auto islet surgery, the patient's islet cells, which produce hormones that regulate the endocrine system, are extracted from the pancreas after it is removed. The cells are then processed and reinfused into the patients liver. When auto islet surgery is successful, the reinfused cells produce insulin, acting in place of the pancreas to regulate blood sugar.

The most recent findings show that about one third of patients require no insulin therapy after autologous islet transplantation, another third require some insulin therapy after the procedure, and the procedure is unsuccessful in preventing diabetes in the remaining third.

"The goal of pancreatectomy is to relieve pain," says Dr. Beth Schrope, gastrointestinal surgeon and assistant professor of surgery, NewYork-Presbyterian/Columbia University Medical Center, who specializes in the treatment of pancreatitis. Returning to normal activities and living without pain is a tremendous improvement in patients' quality of life. Now with islet transplantation, theres an added bonusthe possible prevention of diabetes."

NewYork-Presbyterian/Columbia University Medical Center is currently accepting patients for auto islet surgery, through a joint effort of NewYork-Presbyterian/Columbia's Pancreas Center and the Stem Cell Processing and Cell Therapy Laboratory of the Department of Pathology. Patients who need a total pancreatectomy for benign diseases (such as chronic pancreatitis) may be eligible for this procedure to avoid Type 1 diabetes.

NewYork-Presbyterian Hospital/Columbia University Medical Center

NewYork-Presbyterian Hospital/Columbia University Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and its academic partner, Columbia University College of Physicians and Surgeons. NewYork-Presbyterian/Columbia provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian/Morgan Stanley Childrens Hospital, NewYork-Presbyterian Hospital/Westchester Division, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian/Lower Manhattan Hospital. The hospital is also closely affiliated with NewYork-Presbyterian/Lawrence Hospital in Bronxville. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area, according to U.S. News & World Report, and consistently named to the magazines Honor Roll of best hospitals in the nation. For more information, visit http://www.nyp.org.

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New Treatment May Prevent Diabetes After Pancreatitis Surgery

Scientists Report Highly Efficient Method for Making Stem …

At NYU Langone Medical Center, scientists have found a way to boost dramatically the efficiency of the process for turning adult cells into so-called pluripotent stem cells by combining three well-known compounds, including vitamin C.

"This big boost in efficiency gives us an opportunity now to study stem cell programming mechanisms at high resolution," says Matthias Stadtfeld, PhD, assistant professor of cell biology and a member of the Skirball Institute of Biomolecular Medicine and the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center, who led the research."This is a very exciting advance," says Ruth Lehmann, PhD, director of the Kimmel Center for Stem Cell Biology and the Skirball Institute at NYU Langone and chair of the Department of Cell Biology. "The new technology developed by the Stadtfeld lab to reprogram differentiated cells efficiently and effectively brings the prospect of stem cell technology for safe use in regenerative medicine ever so much closer."

The standard method for reprogramming skin, blood, or other tissue-specific cell types into "induced pluripotent stem cells" (iPSCs) was reported in 2006 by the laboratory of Kyoto University's Shinya Yamanaka, who later won a Nobel Prize for the achievement. The method involves the artificial expression of four key genes dubbed OKSM (for Oct4, Klf4, Sox2 and myc) whose collective activity slowly prods cells into an immature state much like that of an early embryonic cell. In principle, one could take a sample of cells from a person, induce the cells to become iPSCs, then multiply the iPSCs in a lab dish and stimulate them to mature towards desired adult cell types such as blood, brain or heartwhich then could be used to replace injured or diseased tissue in that same individual.

But there are many formidable technical obstacles, among which is the low efficiency of currently used protocols. Converting most cell types into stable iPSCs occurs at rates of 1 percent or less, and the process can take weeks.Researchers throughout the world have been searching for ways to boost this efficiency, and in some cases have reported significant gains. These procedures, however, often alter vital cellular genes, which may cause problems for potential therapies. For the new study, reported online today in Stem Cell Reports, Dr. Stadtfeld and his laboratory team decided to take a less invasive approach and investigate chemical compounds that transiently modulate enzymes that are present in most cells.

"We especially wanted to know if these compounds could be combined to obtain stem cells at high efficiency," Dr. Stadtfeld says.Two of these compounds influence well known signaling pathways, called Wnt and TGF-, which regulate multiple growth-related processes in cells. The third is vitamin C (also known as ascorbic acid). Best known as a powerful antioxidant, the vitamin was recently discovered to assist in iPSC induction by activating enzymes that remodel chromatinthe spiral scaffold for DNAto regulate gene expression.Simon Vidal, a graduate student in the Stadtfeld lab, and Bhishma Amlani, a postdoctoral researcher, looked first at mouse skin fibroblasts, the most common cell type used for iPSC research. Adding to fibroblasts engineered to express OKSM either vitamin C, a compound to activate Wnt signaling, or a compound to inhibit TGF- signaling increased iPSC-induction efficiency weakly to about 1% after a week of cell culture.

Combining any two worked a bit better. But combining all three brought the efficiency to about 80 percent in the same period of time.In another series of experiments the team worked with blood progenitor cells, which usually replace blood cells lost after injury or infection. The OKSM method on its own can slowly convert these cells to stem cells with up to 30 percent efficiency. Using OKSM together with the three compounds brought the efficiency to nearly 100 percent in less than a week. The researchers also achieved nearly 100-percent yield in mouse liver progenitor cells.Dr. Stadtfeld expects that these dramatic increases in conversion rates of adult cells into embryonic-like stem cells will facilitate future studies of the iPSC induction process, simply by making that induction a more predictable event.

"It's just a lot easier this way to study the mechanisms that govern reprogramming, as well as detect any undesired features that might develop in iPSCs," he said.Vitamin C and the two compounds used to manipulate the Wnt and TGF- pathways are widely studied and considered to have few unknown or hazardous effects, the researchers said. By contrast, the use of OKSM has in some cases caused undesired features in iPSCs, such as developmental defects. By making iPSC induction more rapid and efficient, though, Dr. Stadtfeld's new technique might also make the resulting stem cells safer. "Conceivably it reduces the risk of abnormalities by smoothening out the reprogramming process," Dr. Stadtfeld says. "That's one of the issues we're following up."

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Scientists Report Highly Efficient Method for Making Stem ...

Midwest Stem Cell Therapy Center, University of Kansas …

In 2013, the Kansas Legislature and Governor Sam Brownback approved the formation of the Midwest Stem Cell Therapy Center (MSCTC). The center is housed within the University of Kansas Medical Center campus in Kansas City, Kansas. The MSCTC is designed to serve as a hub of adult stem cell therapy, research, and education in the State of Kansas and the adjoining region.

The MSCTC faculty and staff include physicians, scientists, and trainees representing the fields of adult stem cell biology, neurology, oncology, hematology, cardiac and vascular, endocrine, and other subspecialties. These individuals represent several local and regional institutions, enabling the formation of a stem cell network of knowledge and information. This synergy among various institutions also fosters productive collaborations that may result in faster translation of basic science discoveries into the clinic.

It is because of this outstanding team of dedicated members, the MSCTC has made significant strides in the relatively short time since its inception. Indeed, the MSCTC now houses a fully functional GMP operation that has been processing cells for human therapy. One clinical trial with bone marrow cells has been initiated, and several future clinical trials with adult stem cells are in the start-up phase. In addition, cutting edge molecular stem cell research is being conducted by MSCTC scientists. These ongoing studies involve induced pluripotent stem cells, regulation of cellular differentiation, cord blood cells, as well as various transcription factors and other molecular pathways in adult stem cells.

Besides clinical trials and basic research, dissemination of information regarding adult stem cell treatment options for various diseases is a major goal of MSCTC. The web portals for these informational modules are currently under construction. In addition, the MSCTC is planning to expand the training of postdoctoral fellows in basic research in adult stem cell biology, as well as clinicians in adult stem cell-related topics. Our goal is to further broaden the multidisciplinary range of expertise available within MSCTC. Also related to education, the first Midwest Conference on Cell Therapy and Regenerative Medicine was held under the auspices of MSCTC in November 2013. This meeting was extremely well received by the varied audience. We intend to hold the 2014 meeting on Sep 19-20.

Despite this rapid progress, it should be recognized that the MSCTC is a very recent and rather nascent phenomenon. We have a very long way to go. At the same time, we are very stimulated by the support and enthusiasm surrounding the MSCTC - and remain firmly committed to promoting adult stem cell therapy and research - so that patients with often incurable diseases may have hope.

Thank you for visiting. We hope to count on your support toward improving lives with adult stem cells!

Buddhadeb Dawn, M.D. Director, Midwest Stem Cell Therapy Center

Last modified: Apr 24, 2014

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BioTimes Subsidiary Cell Cure Neurosciences Ltd. Demonstrates the Safety and Efficacy of OpRegen in Preclinical …

We are very pleased with the safety data obtained in two animal species that demonstrate that OpRegen cells survive following transplantation for a long period of time and do not result in teratoma formation or any other type of pathology. The efficacy of the OpRegen cells was evaluated in the Royal College of Surgery rat model of retinal degeneration, which is a well-established animal model of retinal degeneration which has been extensively used to evaluate various potential cell therapies. The OpRegen cells were found to remain therapeutically functional over long periods and to maintain the animals visual performance that would normally decay over time in this disease model, said Benjamin Reubinoff, MD, PhD, Chief Scientific Officer of Cell Cure and Chairman of Obstetrics and Gynecology and Director of the Hadassah Human Embryonic Stem Cell Research Center at Hadassah Medical Center, Jerusalem, Israel. Furthermore, the protection of the animals vision from decay was dose dependent. As an additional indicator of therapeutic potential, the number of cone photoreceptors, which are responsible for fine vision in humans and are degenerating in the macula of dry-AMD patients, was found to remain constant over an extended period in the animal model.

We are very pleased with the progress that Cell Cures team has made in preparing for the companys FDA submission, said Charles S. Irving PhD, Cell Cures CEO. We look forward to initiating the clinical trial that will utilize for the first time high quality, xeno-free grade RPE cells for the treatment of geographic atrophy, the severe stage of dry-AMD.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is one of the major diseases of aging and is the leading cause of visual impairment in Americans 55 years of age and older. AMD affects the macula, which is the part of the retina responsible for sharp, central vision that is important for facial recognition, reading and driving. There are two forms of AMD. The dry form (dry-AMD) advances slowly and painlessly until it reaches the severe form called geographic atrophy (GA), which may result in legal blindness. About 10% of patients with dry-AMD develop wet-AMD, which is an acute disease and can lead to blindness in a matter of weeks. Wet-AMD can be treated with currently-marketed angiogenesis inhibitors such as Lucentis or Eylea, however, such products typically require frequent injections, and patients often continue to suffer from the continued progression of the underlying dry-AMD disease process. There is no FDA-approved treatment for dry-AMD for which some seven million people in the US have the intermediate form of the disease and have a high risk for developing GA. The market opportunity for a treatment for GA has been estimated at over $5 billion globally. Current estimated sales of angiogenesis inhibitors for the treatment of the wet form of AMD are estimated to be about $7 billion worldwide. The root cause of the larger problem of dry-AMD is believed to be the degeneration of a particular type of cell in the retina called "retinal pigment epithelial" (RPE) cells. One of the most exciting therapeutic approaches to dry-AMD is the transplantation of healthy, young RPE cells to replace the patients old degenerating RPE cells. One of the most promising sources of healthy RPE cells is from pluripotent stem cells.

About OpRegen

Cell Cure's OpRegen consists of RPE cells that are produced using a proprietary process that drives the differentiation of human embryonic stem cells into high purity RPE cells. OpRegen is also xeno-free", meaning that no animal products were used either in the derivation and expansion of the human embryonic stem cells or in the directed differentiation process. The avoidance of the use of animal products eliminates some safety concerns. OpRegen is formulated as a suspension of RPE cells. Preclinical studies in mice have shown that OpRegen transplanted subretinally as a suspension of cells can rapidly organize into their natural monolayer structure and survive throughout the lifetime of the animal. OpRegen will be an off-the-shelf allogeneic product provided to retinal surgeons in a final formulation ready for transplantation. Unlike treatments that require multiple injections into the eye, such as currently-marketed products like Lucentis and Eylea for wet-AMD, it is expected that OpRegen will be administered in a single procedure.

About Cell Cure Neurosciences Ltd.

Cell Cure Neurosciences Ltd. was established in 2005 as a subsidiary of ES Cell International Pte. Ltd. (ESI), now a subsidiary of BioTime, Inc. (NYSE MKT: BTX). Cell Cures second largest shareholder is HBL Hadasit Bio-Holdings, (TASE: HDST, OTC: HADSY). Cell Cure is located in Jerusalem, Israel on the campus of Hadassah Medical Center. Cell Cure's mission is to become a leading supplier of human cell-based therapies for the treatment of retinal and neural degenerative diseases. Its technology platform is based on the manufacture of diverse cell products sourced from clinical-grade (GMP-compatible) human embryonic stem cells. Its current focus is the development of retinal pigment epithelial (RPE) cells for the treatment of age-related macular degeneration. Cell Cure's major shareholders include BioTime, Inc., HBL Hadasit Bio-Holdings Ltd., Teva Pharmaceuticals Industries Ltd. (NYSE: TEVA), and Asterias Biotherapeutics (OTCBB: ASTY). Additional information about Cell Cure can be found on the web at http://www.cellcureneurosciences.com. A video of a presentation by Cell Cures CEO Dr. Charles Irving is available on BioTimes web site.

About BioTime

BioTime is a biotechnology company engaged in research and product development in the field of regenerative medicine. Regenerative medicine refers to therapies based on stem cell technology that are designed to rebuild cell and tissue function lost due to degenerative disease or injury. BioTimes focus is on pluripotent stem cell technology based on human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells. hES and iPS cells provide a means of manufacturing every cell type in the human body and therefore show considerable promise for the development of a number of new therapeutic products. BioTimes therapeutic and research products include a wide array of proprietary PureStem progenitors, HyStem hydrogels, culture media, and differentiation kits. BioTime is developing Renevia (a HyStem product) as a biocompatible, implantable hyaluronan and collagen-based matrix for cell delivery in human clinical applications, and is planning to initiate a pivotal clinical trial around Renevia, in 2014. In addition, BioTime has developed Hextend, a blood plasma volume expander for use in surgery, emergency trauma treatment and other applications. Hextend is manufactured and distributed in the U.S. by Hospira, Inc. and in South Korea by CJ HealthCare Corporation, under exclusive licensing agreements.

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BioTimes Subsidiary Cell Cure Neurosciences Ltd. Demonstrates the Safety and Efficacy of OpRegen in Preclinical ...

NYU Langone Scientists Report Reliable and Highly Efficient Method for Making Stem Cells

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Newswise NEW YORK, September 18, 2014 Scientists at NYU Langone Medical Center have found a way to boost dramatically the efficiency of the process for turning adult cells into so-called pluripotent stem cells by combining three well-known compounds, including vitamin C.

Using the new technique in mice, the researchers increased the number of stem cells obtained from adult skin cells by more than 20-fold compared with the standard method. They say their technique is efficient and reliable, and thus should generally accelerate research aimed at using stem cells to generate virtually any tissue. Stem cells are immature or uncommitted cells that are theoretically capable of becoming any cell type.

This big boost in efficiency gives us an opportunity now to study stem cell programming mechanisms at high resolution, says Matthias Stadtfeld, PhD, assistant professor of cell biology and a member of the Skirball Institute of Biomolecular Medicine and the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center, who led the research.

This is a very exciting advance, says Ruth Lehmann, PhD, director of the Kimmel Center for Stem Cell Biology and the Skirball Institute at NYU Langone and chair of the Department of Cell Biology. The new technology developed by the Stadtfeld lab to reprogram differentiated cells efficiently and effectively brings the prospect of stem cell technology for safe use in regenerative medicine ever so much closer."

The standard method for reprogramming skin, blood, or other tissue-specific cell types into induced pluripotent stem cells (iPSCs) was reported in 2006 by the laboratory of Kyoto Universitys Shinya Yamanaka, who later won a Nobel Prize for the achievement. The method involves the artificial expression of four key genes dubbed OKSM (for Oct4, Klf4, Sox2 and myc) whose collective activity slowly prods cells into an immature state much like that of an early embryonic cell.

In principle, one could take a sample of cells from a person, induce the cells to become iPSCs, then multiply the iPSCs in a lab dish and stimulate them to mature towards desired adult cell types such as blood, brain or heartwhich then could be used to replace injured or diseased tissue in that same individual.

But there are many formidable technical obstacles, among which is the low efficiency of currently used protocols. Converting most cell types into stable iPSCs occurs at rates of 1 percent or less, and the process can take weeks.

Researchers throughout the world have been searching for ways to boost this efficiency, and in some cases have reported significant gains. These procedures, however, often alter vital cellular genes, which may cause problems for potential therapies. For the new study, reported online today in Stem Cell Reports, Dr. Stadtfeld and his laboratory team decided to take a less invasive approach and investigate chemical compounds that transiently modulate enzymes that are present in most cells. We especially wanted to know if these compounds could be combined to obtain stem cells at high efficiency, Dr. Stadtfeld says.

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NYU Langone Scientists Report Reliable and Highly Efficient Method for Making Stem Cells

Team reports reliable, highly efficient method for making stem cells

10 hours ago A new method resulted in a colony of stem cells, glowing green, derived from one adult immune cell. Credit: Laboratory of Matthias Stadtfeld at NYU Langone Medical center

Scientists at NYU Langone Medical Center have found a way to boost dramatically the efficiency of the process for turning adult cells into so-called pluripotent stem cells by combining three well-known compounds, including vitamin C. Using the new technique in mice, the researchers increased the number of stem cells obtained from adult skin cells by more than 20-fold compared with the standard method. They say their technique is efficient and reliable, and thus should generally accelerate research aimed at using stem cells to generate virtually any tissue. Stem cells are immature or uncommitted cells that are theoretically capable of becoming any cell type.

"This big boost in efficiency gives us an opportunity now to study stem cell programming mechanisms at high resolution," says Matthias Stadtfeld, PhD, assistant professor of cell biology and a member of the Skirball Institute of Biomolecular Medicine and the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center, who led the research.

"This is a very exciting advance," says Ruth Lehmann, PhD, director of the Kimmel Center for Stem Cell Biology and the Skirball Institute at NYU Langone and chair of the Department of Cell Biology. "The new technology developed by the Stadtfeld lab to reprogram differentiated cells efficiently and effectively brings the prospect of stem cell technology for safe use in regenerative medicine ever so much closer."

The standard method for reprogramming skin, blood, or other tissue-specific cell types into "induced pluripotent stem cells" (iPSCs) was reported in 2006 by the laboratory of Kyoto University's Shinya Yamanaka, who later won a Nobel Prize for the achievement. The method involves the artificial expression of four key genes dubbed OKSM (for Oct4, Klf4, Sox2 and myc) whose collective activity slowly prods cells into an immature state much like that of an early embryonic cell.

In principle, one could take a sample of cells from a person, induce the cells to become iPSCs, then multiply the iPSCs in a lab dish and stimulate them to mature towards desired adult cell types such as blood, brain or heartwhich then could be used to replace injured or diseased tissue in that same individual.

But there are many formidable technical obstacles, among which is the low efficiency of currently used protocols. Converting most cell types into stable iPSCs occurs at rates of 1 percent or less, and the process can take weeks.

Researchers throughout the world have been searching for ways to boost this efficiency, and in some cases have reported significant gains. These procedures, however, often alter vital cellular genes, which may cause problems for potential therapies. For the new study, reported online today in Stem Cell Reports, Dr. Stadtfeld and his laboratory team decided to take a less invasive approach and investigate chemical compounds that transiently modulate enzymes that are present in most cells. "We especially wanted to know if these compounds could be combined to obtain stem cells at high efficiency," Dr. Stadtfeld says.

Two of these compounds influence well known signaling pathways, called Wnt and TGF-, which regulate multiple growth-related processes in cells. The third is vitamin C (also known as ascorbic acid). Best known as a powerful antioxidant, the vitamin was recently discovered to assist in iPSC induction by activating enzymes that remodel chromatinthe spiral scaffold for DNAto regulate gene expression.

Simon Vidal, a graduate student in the Stadtfeld lab, and Bhishma Amlani, a postdoctoral researcher, looked first at mouse skin fibroblasts, the most common cell type used for iPSC research. Adding to fibroblasts engineered to express OKSM either vitamin C, a compound to activate Wnt signaling, or a compound to inhibit TGF- signaling increased iPSC-induction efficiency weakly to about 1% after a week of cell culture. Combining any two worked a bit better. But combining all three brought the efficiency to about 80 percent in the same period of time.

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Team reports reliable, highly efficient method for making stem cells

Stem Cell Research – The UT Health Science Center at …

From trying to create new cartilage in the laboratory to clinical trials for patients with brain injuries, scientists and physicians at The University of Texas Health Science Center at Houston (UTHealth) are leading the way in stem cell research.

In partnership with Memorial Hermann-Texas Medical Center, UTHealth was the first in the country to intravenously inject a stroke patients own stem cells in a trial funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. Learn how researchers continue to push the boundaries of this promising field.

UTHealth specialists available for interview

A first-of-its-kind clinical trial studying two forms of stem cell treatments for children with cerebral palsy (CP) has begun at The University of Texas Health Science Center at Houston (UTHealth) Medical School.

Sean I. Savitz, M.D., associate professor of neurology at The University of Texas Health Science Center at Houston (UTHealth), recently received the Molly and Bernard Sanberg Memorial Award from the American Society of Neural Therapy and Repair (ASNTR).

Every year, approximately 795,000 people in the United States suffer a stroke and the late U.S. Senator and Democratic Party vice presidential candidate Lloyd Bentsen was one of them. As the senator and his wife, B. A., dealt with the challenges of stroke, they developed the idea for a stroke research center.

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Stem Cell Research - The UT Health Science Center at ...