“Latest Stem Cells News”

While applications of induced pluripotent stem cells in stem cell therapy may be limited to a few diseases, its applications in drug discovery are wide-ranging, and many more diseases can be targeted, Shinya Yamanaka, Director, Centre for iPS Cell Research and Application, Japan, has said.

The Japanese scientist, whose breakthrough was the creation of embryonic-like stem cells from adult skin cells, believes that the best chance for stem cell therapy lies in offering hope to those suffering from a few conditions, among them, macular disease, Type 1 Diabetes, and spinal cord injuries.

On the other hand, there were multiple possibilities with drug discovery for a range of diseases, and Prof. Yamanaka was hopeful that more scientists would continue to use iPS for studying this potential.

He currently serves as the Director of the Center for iPS Cell Research and Application and as Professor at the Institute for Frontier Medical Sciences at Kyoto University. He is also a Senior Investigator at the University of California, San Francisco (UCSF) – affiliated J. David Gladstone Institutes.

An invited speaker of the CellPress-TNQ India Distinguished Lectureship Series, co-sponsored by Cell Press and TNQ Books and Journals, Prof. Yamanaka spoke to a Chennai audience on Tuesday evening about those “immortal” cells, that he originally thought would take “forever” to create, but actually took only six years.

“My fixed vision for my research team was to re-programme adult cells to function like embryonic-like stem cells. I knew it could be done, but just didn’t know how to do it,” Prof. Yamanaka said.

Embryonic stem cells are important because they are pluripotent, or possess the ability to differentiate into any other type of cell, and are capable of rapid proliferation. However, despite the immense possibilities of that, embryonic cells are a mixed blessing: there are issues with post-transplant rejection (since they cannot be used from a patient’s own cells), and many countries of the world do not allow the use of human embryos.

Dr. Yamanaka’s solution would scale these challenges if only he and his team could find a way to endow non-embryonic cells with those two key characteristics of embryonic stem cells.

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What is a neural stem cell? How can they help treat neurological disorders such as Alzheimer’s disease, Parkinson’s disease, spinal cord injury, stroke, ALS (Lou Gehrig‘s Disease)? Evan Snyder of the Burnham Institute helps define neural stem cells (NSC), explaining that they are relatively inaccessible in the adult patient, but that they seem to benefit from some immunotolerance.

It follows that we may be able to use readily available lines of embryonic stem cells for therapy in neurodegenerative disease. Evan reviews current clinical applications for neural stem cells (including as a vehicle for small molecule delivery), and gives his future outlook for neural stem cells. Evan forsees NSCs being used in anti-inflammatory and neuroprotective functions, to deliver tumor killing genes, and to build iPS drug discovery models.

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Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed.

Collaborators from Harvard University, Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain.

Repair at the cellular-level of the hypothalamus — a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression — indicates the possibility of new therapeutic approaches to even higher-level conditions such as spinal cord injury, autism, epilepsy, ALS  (Lou Gehrig’s disease), Parkinson’s disease, and Huntington’s disease.

“There are only two areas of the brain that are known to normally undergo ongoing large-scale neuronal replacement during adulthood on a cellular level — so-called ‘neurogenesis,’ or the birth of new neurons — the olfactory bulb and the subregion of the hippocampus called the dentate gyrus, with emerging evidence of lower level ongoing neurogenesis in the hypothalamus,” said Jeffrey Macklis, Harvard University professor of stem cell and regenerative biology and HMS professor of neurology at MGH, and one of three corresponding authors on the paper. “The neurons that are added during adulthood in both regions are generally smallish and are thought to act a bit like volume controls over specific signaling.  Here we’ve rewired a high-level system of brain circuitry that does not naturally experience neurogenesis, and this restored substantially normal function.”

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Emory University researchers are participating in a groundbreaking clinical trial to treat patients with amyotrophic lateral sclerosis (ALS) using human neural stem cells.

The Phase 1 trial, will assess the safety of stem cells, and the surgical procedures and devices required, for multiple injections of the cells directly into the spinal cord.

“This is the first U.S. clinical trial of stem cell injections into the spinal cord for the treatment of ALS,” says principal researcher Jonathan Glass, professor of neurology in the School of Medicin, and director of the Emory ALS Center. “Our main goal in this early phase is to determine whether it is safe to inject stem cells into the spinal cord and whether the cells themselves are safe.”

Three patients with ALS have received injections since the trial began in January. Up to twelve individuals will be enrolled at in this phase of the trial.

Nicholas Boulis, assistant professor of neurosurgery I the School of Medicine and a pioneer in developing surgical methods for delivery of therapeutics to the spinal cord, is performing the surgical procedures.

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Neuralstem Inc. has received the green light to begin the first human stem cell trial to treat Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig’s disease. The company’s stock soared on the news.

Neuralstem has only received approval for the first stage of the trial that would consist of 12 patients who will receive stem cell injections in the lumbar area of the spinal cord.

Neuralstem said the trial will be under the direction of principal investigator Dr. Eva L. Feldman, Director of the University of Michigan Health System ALS Clinic and the Program for Neurology Research & Discovery. Feldman called the trial a major step forward in the treatment of ALS. “In work with animals, these spinal cord stem cells both protected at-risk motor neurons and made connections to the neurons controlling muscles. We don’t want to raise expectations unduly, but we believe these stem cells could produce similar results in patients with ALS,” Dr. Feldman said.

from

http://washington.bizjournals.com/washington/stories/2009/09/21/daily7.html

http://www.reuters.com/article/americasRegulatoryNews/idUSBNG36053620090921

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Emory University researchers have received approval from the Food and Drug Administration (FDA) to advance to the next phase of a landmark trial to treat patients with Amyotrophic Lateral Sclerosis (ALS) using human neural stem cells.

The Phase I trial, currently underway exclusively at Emory University, is designed to assess the safety of implanting neural stem cells into the spinal cord in up to 18 people with ALS and began in January 2010. The first 12 patients received neural stem cell transplants in the lumbar, or lower, region of the spinal cord. After reviewing safety data from these patients, the FDA has granted approval for the trial to advance to the final two groups of patients (three in each group), all of who will be transplanted in the cervical, or upper, region of the spinal cord.

“This represents a major accomplishment for the trial, meaning that we have achieved our stated goal of proving safety in the first 12 patients who received lumbar spinal injections,” says Jonathan Glass, MD, Professor of Neurology, Emory School of Medicine and director of the Emory ALS Center.

“Our next objective is to demonstrate that we can deliver the cells safely to the cervical spinal cord, which is particularly important because therapy in this region may help patients better maintain their ability to breathe.”

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