“Latest Stem Cells News”

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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Patents offer the economic guarantees scientists and companies need to develop new treatments, Oliver Bruestle told Deutsche Welle. He’s at the center of a German court battle surrounding embryonic stem cell research

Oliver Bruestle, director of the Institute of Reconstructive Neurobiology at the University of Bonn, is pushing for Germany to recognize the right to patent procedures conducted on embryonic stem cells, saying patents are the right way to ensure that scientists and companies profit from their work.

Greenpeace, however, is opposed to the patents. The organization filed suit against a patent granted to Bruestle in 1999, saying that the patenting of embryonic stem cell research could lead to an “embryo industry.” (…)

There is obviously a lot of hope and hype attached to embryonic stem cell research. Some people imagine a world full of bionic limbs and clones. Is that where the research is headed?

Stem cell research has huge potential for biomedicine mainly because there’s an opportunity to generate essentially every single type of body cell and every single type of tissue artificially in a cell culture lab. This is particularly relevant for organs which have lost their capacity for regeneration. That’s true for the nervous system and the heart as well as for insulin-producing cells. For these tissues, embryonic stem cell lines, which are really the entry point of the patent and procedure, provide a limitless source of cells. We can use these cells to generate insulin-producing cells, heart cells and brain cells in limitless numbers in a cell culture dish (…)

There’s also a lot of fear for people who envision a world full of bionic limbs and organs and clones. Is there potential for this to get out of hand?

There are quite a few misconceptions in the field. For example, we get confronted with accusations that we do research on embryos. This is, in fact, not true. The way the research is done is that there is a possibility to derive what we call embryonic stem cell lines from oocytes, which have been fertilized during artificial insemination or during fertility treatments which are left over and frozen and which are otherwise thrown away in large numbers.

There is an opportunity to use these cells with consent of the parents to derive embryonic stem cell lines and the very special things about these stem cell lines is once they are derived they can be multiplied indefinitely. We can grow them for years, we can freeze them, we can thaw them and they have the remarkable potential that they can be turned into any type of cell in our body.

This field needs a very clear and tight regulation. We certainly have such a situation in Germany. We have one of the toughest embryo protection acts in the world, which essentially prohibits any procedure which is not to the benefit of the embryo. That’s the reason why in Germany we cannot derive embryonic stem cells from fertilized oocytes, which can be done in many other countries (…)

What other possibilities does stem cell research offer that could improve people’s lives?

The prime candidates for stem cell therapies in the nervous system are diseases which lead to a loss of nerve cells or other cells in defined areas. For example, Parkinson’s disease and Huntington’s disease are diseases where we see the loss of very specific types of nerve cells in very specific areas. For replacement therapy, we know where to go and which cell type to put in (…)

from http://www.dw-world.de/dw/article/0,,4898622,00.html

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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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The same genes that are chemically altered during normal cell differentiation, as well as when normal cells become cancer cells, are also changed in stem cells that scientists derive from adult cells, according to new research from Johns Hopkins and Harvard.

Although genetically identical to the mature body cells from which they are derived, induced pluripotent stem cells (iPSCs) are notably special in their ability to self-renew and differentiate into all kinds of cells. And now scientists have detected a remarkable if subtle molecular disparity between the two: They have distinct “epigenetic” signatures; that is, they differ in what gets copied when the cell divides, even though these differences aren’t part of the DNA sequence.

“Relatively little study has been done on the epigenetic nature of stem cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine at the Johns Hopkins University School of Medicine. “To date, the bulk of what is known about stem cells is focused on how you create them and grow them and so forth, but not on the essence of them, and what is fundamentally different about these cells.”

To compare and contrast mature connective tissue cells called fibroblasts with the pluripotent stem cells into which they were reprogrammed, the investigators focused on a chemical change known as methylation. This chemical change which, associated with silencing genes, is classified as epigenetic because, although not part of the DNA sequence, is copied when a cell divides. They identified and then measured so-called differentially methylated regions (DMRs) of genes whose expression was changed in the process of being reprogrammed from a parent cell to a stem cell.

Building on previous research that looked at where differently methylated sites were located in cancer cells, as well as on research that had shown these same sites matching up with many of the methylated areas that had been implicated in the differentiation of normal brain, liver and spleen tissues, the team discovered that the reprogramming of a cell to become a stem cell apparently involves many of the very same DMRs and genes.

“The surprise,” says Feinberg, “is that there is such a degree of overlap between the differently methylated regions and genes that are involved in turning a fibroblast into a stem cell and turning a normal cell into a cancer cell.”

The study, done jointly with George Q. Daley, M.D., Ph.D., and colleagues from Harvard University, was published Nov. 1 in the advanced online edition of Nature Genetics. The researchers suggest in the study that certain sites throughout the genome appear to be generally involved in distinguishing DNA methylation among different cell types and cancers, and these same sites are involved in reprogramming fibroblasts back into stem cells (…)

from http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20091104.074444&time=09%2059%20PST&year=2009&public=0

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Adult stem cells tested for defects before being implanted in the injured spinal cords of mice helped the animals recover with no cancerous side effects, according to new research. In recent years, scientists found that some experimental stem cell therapies can cause cancerous tumors. Pre-screened cells could result in potentially life- saving treatments without such side effects.

These new findings were presented at Neuroscience 2009, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health. “We tried to identify induced pluripotent stem cells from adult tissue that would be safe when applied to cell therapy for central nervous system disorders,” said Masaya Nakamura, MD, PhD, at Keio University School of Medicine, a co-author of the study. “These results suggest that properly pre-evaluated cells may be a promising source for future transplantation therapy.”

Here, the authors investigated the possibility of making transplantation therapies safer and more efficient by examining different types of stem cells. They generated 36 induced pluripotent stem cell clones, which differed in their origins and other characteristics. They found that the cell’s origin was a crucial indicator of whether the cells would result in tumors.

Results showed that immature (undifferentiated) stem cells are more likely to form tumors than mature ones. The transplantation of “safe” cells into mice with spinal cord injuries resulted in the formation of new neurons, while “unsafe” cells sped recovery for a short period but ultimately formed tumors.

“This study confirms that before human clinical trials go forward involving treatment of central nervous system disorders with induced pluripotent stem cells, pre-evaluating each cell clone carefully is essential,” Nakamura said.

from http://www.sciencedaily.com/releases/2009/10/091022115618.htm

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Researchers and using stem cells as tools for disease study, drug screening, clinical trial strategy, and personalized medicine. The induced Pluripotent Stem cell (iPS) is giving us a chance to rethink the way we are developing new drugs. These iPS cells are usually created from somatic cells (such as skin), and not embryos or adult stem cells. In creating iPS from patients’ diseased cells, scientists can study the disease in vitro, looking for disease phenotypes, applying microenvironmental stress, and testing new drugs. Compared to animal model testing (e.g. mice), this represents a significant breakthrough, that can be used to validate clinical development strategy and test efficacy in specific groups of patients. iPS is bringing a revolution in drug discovery methodology which is being used to bridge genetics, cell biology, and physiology.

from http://biobusiness.tv/videos/208

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