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Stem Cell Grafts Promote Myelination in an Animal Study

Shaw, Gina

doi: 10.1097/01.NT.0000423164.31970.1d


The myelination findings in the clinical trial here mirror those established in a companion preclinical study using transgenic Shiverer-immunodeficient mice, led by Stephen A. Back, MD, PhD, associate professor of pediatrics at Oregon Health and Science University's Doernbecher Children's Hospital. The study, which was also sponsored by Stem Cells, Inc., was published in the same issue of Science Translational Medicine.

Prior to this study, stem cell transplants had been primarily studied in newborn mice, whose brains respond very well to such infusions. “But in patients, that's not the situation we'll be testing,” Dr. Back said. “We won't be transplanting stem cells into newborns, but into children and adults who are in a more advanced stage of the disease at time of transplant.” Dr. Back's study was the first to implant true human brain-derived stem cells into animals that were already deteriorating neurologically.

Using high-field MRI, Dr. Back and his colleagues were able to identify areas of the brain where myelin had formed. “We found that the stem cells preferentially matured into myelin-forming cells as opposed to other types of brain cells in both newborn mice and older mice. The brain-derived stem cells appeared to be picking up on cues in the white matter that instructed the cells to become myelin-forming cells,” he said. “And though we were transplanting the cells into neurologically advanced animals with very shortened lifespans, we demonstrated that by the time the myelin was quite mature, there was considerable mapping of myelin around axons, and it increased conductivity across the corpus callosum. So it was not only structurally normal but functionally normal as well.”

At autopsy, the scientists found that the human cell-derived myelin was indeed in the area of the mouse brains where they had detected advanced signal from MRI readings — supporting the idea that MRI is an effective tool for detecting stem cell derived myelin proliferation in the human brain as well.

Steven Goldman, MD, PhD, professor and emeritus chair of neurology at the University of Rochester School of Medicine and co-director of its Center for Translational Neuromedicine, questioned whether neural stem cells were optimal for this particular disease target. “Most successful animal studies have used defined and lineage-restricted glial progenitor cells,” he said. “The problem with neural stem cells is that they don't migrate as efficiently in postnatal brain tissue. They give rise to lots of astrocytes and neurons, depending on where they're put and the disease environment. I'd say the jury is still out as to whether neural stem cells can be as good a clinical vector as glial progenitor cells, but they are the type of cells in which the company chose to invest.”

Dr. Goldman disclosed that he is an inventor on patents held by the University of Rochester and/or Cornell University for non-human animals with human glial chimeric brains, myelination of congenitally dysmyelinated forebrains using oligodendrocyte progenitor cells, and a method for isolating and purifying oligodendrocytes and oligodendrocyte progenitor cells.



©2012 American Academy of Neurology