This special journal news summary reflects emerging concepts on stem cells to dovetail with the discussions at ALSA’s workshop on stem cells held at Cold Spring Harbor September 12-14. Please see ALSA’s web site for monthly journal news updates that reflect progress in ALS research.
Stem Cells Living in Lab Dishes Show Genetic Changes Over TimeIn the September 4 online edition of Nature Genetics, a large collaborative multinational group led by Johns Hopkins researcher Aravinda Chakravarti, Ph.D., and NIH scientist Mahendra Rao, Ph.D.,demonstrated that stem cells growing in the lab can accumulate genetic changes that could render them unsafe for therapeutic use. Some of the changes resemble those seen in cancers. The researchers noted that those stem cells cultured for short periods are free of such changes and emphasized the need to monitor lab grown stem cells for genetic integrity.
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Spinal Cord Repair with Adult Human Neural Stem CellsMice with damaged spinal cords could regain some function after a transplant of human neural stem cells, according to a report in the September 19 online Proceedings of the National Academy of Sciences by Brian Cummings, Ph.D., and colleagues at the University of California in Irvine. The mice once again lost their ability to coordinate walking when treated with diphtheria toxin which only kills human cells so this showed their recovery was due to the human graft. The researchers showed that the implanted cells formed both neurons and their support cells called glia. This approach may have only limited relevance to ALS as spinal cord injury is to a known place on the cord, and ALS is caused by as yet unknown processes that kill motor neurons in many different places in the nervous system.
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Repair of Damaged Spinal Cord with Rat Embryo Stem CellsRats with damage to the spinal cord from trauma could regain motor skill and showed transmission of electrical signals after a transplant of cells from rat embryos that are able to turn into the supportive cells of the nervous system called glia. The glial cells can form the insulating sheath (called myelin) around nerves to allow the rapid transmission of signals necessary for muscles to contract. The researchers working with Scott R. Whittemore, Ph.D., at the Kentucky Spinal Cord Injury Research Center at the University of Louisville first used a gene therapy to boost the glial cells’ production of growth promoting factors and then placed the engineered cells into the injured rats as reported in the July 2005 issue of the Journal of Neuroscience. ALSA funded researchers are using similar strategies to create stem cell based therapy to repair damage in ALS.
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Important Nerve Cell Messenger Also Controls Neural Stem CellsThe nerve cell messenger GABA (for gamma amino butyric acid) provides feedback to say how many neural stem cells are needed as the brain forms, researchers reported in the August 28 online edition of Nature Neuroscience. This important signal normally tells neurons not to fire. Apparently GABA is also able to be released by stem cells before the actual synaptic connections are made in the developing brain. Thus GABA can regulate how many new cells form and deploy before it functions as a neurotransmitter. Researchers Angelique Bordey, Ph.D., at Yale and colleagues show that the generation of stem cells like so many other processes in the nervous system operates with feedback control—once there is enough, the substance itself slows its own production. Knowing that GABA is an important stem cell regulator will help researchers study how stem cells might be used as therapy for ALS.
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Master Switches Identified for Stem CellsThe key genes that keep stem cells able to produce all the cell types in the body do so by keeping other genes silent. The hierarchy of genes important to the stem cell state is detailed in a report in the September 8 online edition of Cell. Douglas Melton Ph.D. at Harvard and Rudolf Jaenisch, M.D. at the Whitehead Institute and the Massachusetts Institute of Technology and their colleagues show that three proteins, called Oct4, Sox2, and Nanog, suppress cascades of genes that must turn on to effect the creation of an embryo from its stem cells. Details such as these on how stem cells produce all other cells will allow further progress in using stem cells in regenerative medicine.
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Recipe for Neural Stem Cells in Lab DishesResearchers in Europe published a new way to grow pure neural stem cells in the lab, keeping the cells in the stem cell state but without requiring formation of the clusters of cells called neurospheres. Reporting September in the Public Library of Science Biology online journal, Austin Smith, Ph.D., of the University of Edinburgh, U.K. and Elena Cattaneo, Ph.D., of the University of Milan, Italy and colleagues show that adding fibroblast growth factor 2 and epidermal growth factor allows neural stem cells from mouse or human embryonic stem cells to keep multiplying indefinitely in lab dishes. These pure neural stem cells can be placed successfully in the adult mouse brain to become neurons or their supporting glial cells. This advance should allow researchers to more easily study and manipulate these important cell precursors to produce all the types of cells in the nervous system.
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Umbilical Cord Might be Source for Embryonic Stem CellsThe cord blood of newborns contains stem cells that might be used therapeutically if they can be identified, isolated, and stored in quantity. Researchers led by Colin McGuckin Ph.D. at Kingston University in Britain collaborating with investigators at the University of Texas Medical Branch in Galveston published a plan for doing so, in the August issue of the journal Cell Proliferation. They were able to isolate from cord blood those cells with identifying markers and other characteristics that showed they were embryonic stem cells, and maintained the cells successfully in laboratory culture. The team used bioreactors made by Synthecon Corp. to grow the stem cells.
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Researchers Find Switch to Turn on MyelinThe neuroregulin gene directs Schwann cells to produce myelin, the insulation that helps motor neurons fire efficiently, according to findings reported in the September issue of Neuron. New York University researchers led by James L. Salzer, M.D., Ph.D., found that this gene actually turns on production of the rolls of myelin, whereas unmyelinated neurons do not express neuregulin. Adding neuregulin to those neurons that are not normally insulated produces myelin. These findings are from peripheral nerves, so the NYU researchers will be looking next at the central nervous system. Knowing the signals that prompt helper cells to wrap around axons and sheath them with myelin may help investigators trying to limit the damage in ALS. Therapies aimed at neuregulin expressin might be able to protect nerve fibers still alive, or might even guide regrowth.
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