Category Archives: Stem Cells

ROCHESTER, Minn. - Every year, about 1,000 babies are born in the United States with half a heart - a rare defect that requires a series of risky surgeries and, even then, leaves the infants with a strong likelihood that their hearts will wear out prematurely.

Now, the Mayo Clinic has received federal approval for a first-of-its kind clinical study to see if stem cells from the babies' own umbilical cords can strengthen their underdeveloped hearts and extend their lives.

If it works, the new technique could buy these children time as scientists scramble for a cure for the congenital defect called hypoplastic left heart syndrome (HLHS).

The Mayo study, which will begin as soon as 10 eligible candidates can be enrolled, could also pave the way for additional breakthroughs in stem cell treatments that would help the 19,000 children born each year with other heart defects. But for the time being, the doctors at Mayo are keeping their focus on those babies who need the most help now.

"We are not here to build an academic career out of science and technology," said Dr. Timothy Nelson, director of Mayo's HLHS research program. "We're really here to make a difference in children's lives who are living today with unmet needs."

Christina DeShaw of Clive, Iowa, was pregnant with fraternal twins when she learned during an ultrasound procedure that the left side of her daughter's heart was not developing properly.

"The world just started spinning," DeShaw said. "Our lives were forever changed from that moment on."

DeShaw and her husband, Brad Weitl, sought help from the Mayo Clinic for the baby they named Ava Grace.

They learned that children born with defects on the left side of the heart must undergo a series of three complex surgeries. The first is called the Norwood procedure: Within a few days of birth, surgeons reconstruct the heart so that the fully developed right ventricle can do both its own work of supplying blood to the lungs and the work of the defective left ventricle, which ordinarily would pump oxygenated blood back to the body.

Dr. Harold Burkhart, who is overseeing surgeries in Mayo's new study, said that when the procedure was developed in 1983, only about 30 percent of the patients survived. About 70 percent survive now, he said, and at Mayo, about nine out of 10 make it through.

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Mayo Clinic puts stem cells to the test on infant heart defect

Newswise University Hospitals Case Medical Center clinical researchers have launched an innovative clinical trial, unique in its design, which will evaluate the ability of a patients own stem cells to prevent leg amputations in end stage peripheral arterial disease (PAD).

Led by Vik Kashyap, MD, Division Chief, Vascular Surgery at University Hospitals Case Medical Centers Harrington Heart & Vascular Institute and Professor of Surgery at Case Western Reserve University School of Medicine, the clinical trial is designed to improve blood flow in legs with blocked arteries by attempting to treat diseased blood vessels. Peripheral arterial disease (PAD) is a common yet serious disease that occurs when extra cholesterol and fat circulating in the blood collects on the walls of the arteries that supply blood to the limbs.

Due to the location and extent of the blockages in certain individuals, standard treatments such as surgical bypass (insertion of a vein or synthetic graft to redirect blood flow around the blockage) and angioplasty (insertion of a balloon through the artery to open the blockage) will not improve blood flow to the leg, and amputation is the only alternative.

For patients with critical limb ischemia (CLI) revascularization procedures such as surgical bypass or percutaneous angioplasty/stenting are currently the only option to restore perfusion and maintain limb viability.

For CLI patients who are non-candidates for revascularization, amputation is often needed. It is estimated that over 160,000 amputations are performed in the United States each year.

The number of CLI patients who will not be candidates for revascularization continues to rise as the population ages and the incidence of diabetes and other vascular risk factors increase. For CLI patients who are considered unreconstructable, the amputation and mortality rates at six months approach 40% and 20%, respectively. Furthermore, nearly 30% of patients who undergo below-knee amputation will fail rehabilitation and require chronic institutional care or professional assistance at home.

The trial sponsor, Biomet Biologics (Warsaw, IN), recently completed a Phase I study of 30 subjects to evaluate the safety of autologous concentrated bone marrow aspirate for critical limb ischemia. The results of this study were used to advance the companys MarrowStim concentration technology into the FDA-approved, pivotal IDE trial described here. Overall, the trial will enroll 152 subjects at up to 20 investigational sites.

This trial offers an opportunity to save a patients leg when there are no remaining options to improve blood supply, said Dr. Kashyap. We are pleased to add this capability at UH and provide hope for patients facing the risk of limb loss.

Subjects will be randomized to receive either the investigational treatment involving the MarrowStim P.A.D. Kit (75% chance), or a placebo control involving a sham procedure (25% chance). The trials primary end point of time to treatment failure, defined as major amputation or death, will be evaluated over a oneyear followup period. Secondary end points, including rest pain, perfusion measurements, quality of life, and safety, will also be evaluated for one year.

Only those patients meeting the pre-defined approved inclusion/exclusion criteria are eligible for this clinical trial. To learn more about this clinical trial and to see the qualifications for participation, visit http://www.clinicaltrialspotlight.com or call toll-free at 877-788-3972.

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University Hospitals Case Medical Center Launches Novel Clinical Trial Using Stem Cells to Prevent Amputation

June 19, 2013 A new study examining the brains of fruit flies reveals a novel stem cell mechanism that may help explain how neurons form in humans. A paper on the study by researchers at the University of Oregon appeared in the online version of the journal Nature in advance of the June 27 publication date.

"The question we confronted was 'How does a single kind of stem cell, like a neural stem cell, make all different kinds of neurons?'" said Chris Doe, a biology professor and co-author on the paper "Combinatorial temporal patterning in progenitors expands neural diversity."

Researchers have known for some time that stem cells are capable of producing new cells, but the new study shows how a select group of stem cells can create progenitors that then generate numerous subtypes of cells.

"Instead of just making 100 copies of the same neuron to expand the pool, these progenitors make a whole bunch of different neurons in a particular way, a sequence," Doe said. "Not only are you bulking up the numbers but you're creating more neural diversity."

The study, funded by the Howard Hughes Medical Institute and the NIH National Institute of Child Health and Human Development, builds on previous research from the Doe Lab published in 2008. That study identified a special set of stem cells that generated neural progenitors. These so-called intermediate neural progenitors (INPs) were shown to blow up into dozens of new cells. The research accounted for the number of cells generated, but did not explain the diversity of new cells.

"While it's been known that individual neural stem cells or progenitors could change over time to make different types of neurons and other types of cells in the nervous system, the full extent of this temporal patterning had not been described for large neural stem cell lineages, which contain several different kinds of neural progenitors," said lead author Omar Bayraktar, a doctoral student in developmental neurobiology who recently defended his dissertation.

The cell types in the study, Bayraktar said, have comparable analogs in the developing human brain and the research has potential applications for human biologists seeking to understand how neurons form.

The Nature paper appears alongside another study on neural diversity by researchers from New York University. Together the two papers provide new insight into the processes involved in producing the wide range of nerve cells found in the brains of flies.

For their study, Bayraktar and Doe zeroed in on the stem cells in drosophila (fruit flies) known as type II neuroblasts. The neuroblasts, which had previously been shown to generate INPs, were shown in this study to be responsible for a more complex patterning of cells. The INPs were shown to sequentially generate distinct neural subtypes. The research accounted for additional neural diversity by revealing a second axis in the mechanism. Instead of making 100 neurons, as had been previously thought, a stem cell may be responsible for generating some 400 or 500 neurons.

The study concludes that neuroblasts and INP patterning act together to generate increased neural diversity within the central complex of the fruit fly and that progenitors in the human cerebral cortex may use similar mechanisms to increase neural diversity in the human brain. One long-term application of the research may be to eventually pinpoint stem cell treatments to target specific diseases and disorders.

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How neural stem cells create new and varied neurons

June 17, 2013 A team from the New York Stem Cell Foundation (NYSCF) Research Institute and the Naomi Berrie Diabetes Center of Columbia University has generated patient-specific beta cells, or insulin-producing cells, that accurately reflect the features of maturity-onset diabetes of the young (MODY).

The researchers used skin cells of MODY patients to produce induced pluripotent stem (iPS) cells, from which they then made beta cells. Transplanted into a mouse, the stem cell-derived beta cells secreted insulin in a manner similar to that of the beta cells of MODY patients. Repair of the gene mutation restored insulin secretion to levels seen in cells obtained from healthy subjects. The findings were reported today in the Journal of Clinical Investigation.

Previous studies have demonstrated the ability of human embryonic stem cells and iPS cells to become beta cells that secrete insulin in response to glucose or other molecules. But the question remained as to whether stem cell-derived beta cells could accurately model genetic forms of diabetes and be used to develop and test potential therapies.

"We focused on MODY, a form of diabetes that affects approximately one in 10,000 people. While patients and other models have yielded important clinical insights into this disease, we were particularly interested in its molecular aspects -- how specific genes can affect responses to glucose by the beta cell," said co-senior author Dieter Egli, PhD, Senior Research Fellow at NYSCF, who was named a NYSCF-Robertson Stem Cell Investigator in 2012.

MODY is a genetically inherited form of diabetes. The most common form of MODY, type 2, results in a loss-of-function mutation in one copy of the gene that codes for the sugar-processing enzyme glucokinase (GCK). With type 2 MODY, higher glucose levels are required for GCK to metabolize glucose, leading to chronic, mildly elevated blood sugar levels and increased risk of vascular complications.

MODY patients are frequently misdiagnosed with type 1 or 2 diabetes. Proper diagnosis can not only change the patient's course of treatment but affect family members, who were previously unaware that they, too, might have this genetic disorder.

NYSCF scientists took skin cells from two Berrie Center type 2 MODY patients and "reprogrammed" -- or reverted -- them to an embryonic-like state to become iPS cells. To examine the effect of the GCK genetic mutation, they also created two genetically manipulated iPS cell lines for comparison: one fully functional (two correct copies of the GCK gene) and one with complete loss of function (two faulty copies of the GCK gene). They then generated beta cell precursors from the fully functional and loss-of-function iPS cell lines and transplanted the cells for further maturation into immune-compromised mice.

"Our ability to create insulin-producing cells from skin cells, and then to manipulate the GCK gene in these cells using recently developed molecular methods, made it possible to definitively test several critical aspects of the utility of stem cells for the study of human disease," said Haiqing Hua, PhD, lead author on the paper, a postdoctoral fellow in the Division of Molecular Genetics, Department of Pediatrics and Naomi Berrie Diabetes Center at Columbia University and the New York Stem Cell Foundation Research Institute.

When given a glucose tolerance test three months later, mice with MODY beta cells had decreased sensitivity to glucose but a normal response to other molecules that stimulate insulin secretion. This is the hallmark of MODY. Mice with two faulty copies of the GCK gene secreted no additional insulin in response to glucose. When the researchers repaired the GCK mutation using molecular techniques, cells with two restored copies of GCK responded normally to the glucose stress test. Unlike other reported techniques, the researchers' approach efficiently repaired the GCK mutation without introducing any potentially harmful additional DNA.

"Generation of patient-derived beta cells with gene correction could ultimately prove to be a useful cell-replacement therapy by restoring patients' ability to regulate their own glucose. This result is truly exciting," said Susan L. Solomon, Chief Executive Officer of The New York Stem Cell Foundation.

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Researchers demonstrate use of stem cells to analyze causes, treatment of diabetes

June 17, 2013 Exposing developing tissue to low levels of the plastic bisphenol A, commonly known as BPA, is linked to a greater incidence of prostate cancer in tissue grown from human prostate stem cells, a new study finds. The results were presented Monday, June 17, at The Endocrine Society's 95th Annual Meeting in San Francisco.

BPA is a synthetic estrogen that is used to add flexibility to many common products, including food cans and containers, compact discs, eyeglasses, and even baby bottles. It is universally prevalent, and tests indicate that almost everyone has measurable levels of the chemical in their bodies.

The chemical has received a great deal of media attention in recent years because of its potential to increase the risk of disease. The concern about BPA in the human body is that it is an endocrine-disrupting chemical, which means that it alters the body's hormonal balance by replicating the activity of a naturally occurring hormone. In this case, BPA replicates the activity of estrogen. Of greatest concern are BPA's effects on developing fetuses and infants because endocrine-disrupting chemicals are thought to predispose developing cells to later disease.

In this study, investigators used human prostate stem cells from organ donors to grow prostate tissue in a mouse model. They found that early BPA exposure significantly increased the risk of both prostate cancer and a precancerous condition known as prostate epithelial neoplasia, or PIN. The incidence rates for PIN and prostate cancer were:

12 percent of non-BPA exposed tissue

33-45 percent of tissue exposed to BPA

"These results suggest that stem cells are direct BPA targets which may explain the long-lasting effects of this chemical throughout the body," said study lead author Gail S. Prins, Ph.D., professor of physiology and urology at the University of Illinois at Chicago. "They provide the first direct in vivo evidence that developmental exposure to environmentally relevant levels of BPA increases human prostate cancer risk."

Investigators were able to observe the effects of BPA on living prostate tissue by isolating prostate stem cells from young men, then combining these cells with undifferentiated cells called mesenchyme, which, for this study, derived from rat tissue. They then grafted this combined tissue to the kidneys of mice where the tissue developed into human prostate tissue. To simulate human BPA exposure, the investigators fed BPA at levels found in humans to the study mice for the first two weeks of the prostate-tissue formation.

One month after the tissue graft, when the prostate tissue had matured, the investigators administered estrogen and testosterone at elevated levels to the study mice to promote prostate disease.

The National Institutes of Health's National Institute of Environmental Health Sciences funded the study.

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Exposure to low doses of BPA linked to increased risk of prostate cancer in human stem cells

Public release date: 17-Jun-2013 [ | E-mail | Share ]

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

NEW YORK, NY (June 17, 2013) A team from the New York Stem Cell Foundation (NYSCF) Research Institute and the Naomi Berrie Diabetes Center of Columbia University has generated patient-specific beta cells, or insulin-producing cells, that accurately reflect the features of maturity-onset diabetes of the young (MODY).

The researchers used skin cells of MODY patients to produce induced pluripotent stem (iPS) cells, from which they then made beta cells. Transplanted into a mouse, the stem cell-derived beta cells secreted insulin in a manner similar to that of the beta cells of MODY patients. Repair of the gene mutation restored insulin secretion to levels seen in cells obtained from healthy subjects. The findings were reported today in the Journal of Clinical Investigation.

Previous studies have demonstrated the ability of human embryonic stem cells and iPS cells to become beta cells that secrete insulin in response to glucose or other molecules. But the question remained as to whether stem cell-derived beta cells could accurately model genetic forms of diabetes and be used to develop and test potential therapies.

"We focused on MODY, a form of diabetes that affects approximately one in 10,000 people. While patients and other models have yielded important clinical insights into this disease, we were particularly interested in its molecular aspectshow specific genes can affect responses to glucose by the beta cell," said co-senior author Dieter Egli, PhD, Senior Research Fellow at NYSCF, who was named a NYSCFRobertson Stem Cell Investigator in 2012.

MODY is a genetically inherited form of diabetes. The most common form of MODY, type 2, results in a loss-of-function mutation in one copy of the gene that codes for the sugar-processing enzyme glucokinase (GCK). With type 2 MODY, higher glucose levels are required for GCK to metabolize glucose, leading to chronic, mildly elevated blood sugar levels and increased risk of vascular complications.

MODY patients are frequently misdiagnosed with type 1 or 2 diabetes. Proper diagnosis can not only change the patient's course of treatment but affect family members, who were previously unaware that they, too, might have this genetic disorder.

NYSCF scientists took skin cells from two Berrie Center type 2 MODY patients and "reprogrammed"or revertedthem to an embryonic-like state to become iPS cells. To examine the effect of the GCK genetic mutation, they also created two genetically manipulated iPS cell lines for comparison: one fully functional (two correct copies of the GCK gene) and one with complete loss of function (two faulty copies of the GCK gene). They then generated beta cell precursors from the fully functional and loss-of-function iPS cell lines and transplanted the cells for further maturation into immune-compromised mice.

"Our ability to create insulin-producing cells from skin cells, and then to manipulate the GCK gene in these cells using recently developed molecular methods, made it possible to definitively test several critical aspects of the utility of stem cells for the study of human disease," said Haiqing Hua, PhD, lead author on the paper, a postdoctoral fellow in the Division of Molecular Genetics, Department of Pediatrics and Naomi Berrie Diabetes Center at Columbia University and the New York Stem Cell Foundation Research Institute.

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NYSCF and Columbia researchers demonstrate use of stem cells to analyze causes, treatment of diabetes