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Stem Cell-Based Therapy for Radiation’s Side Effects on Brain Function

A recent paper from Viviane Tabar’s lab at Memorial Sloan Kettering demonstrates the healing powers of stem cell-derived oligodendrocyte progenitor cells (OPCs) in restoring brain function following radiation. Radiation of the brain is commonly used to treat a number of different cancers, but in some patients this results in long-term side effects including cognitive deficits and motor and balance deficits. Loss of one specific cell type, oligodendrocytes and their progenitors, is thought to underlie part of the problem. Oligodendrocytes produce the myelin that serves as an insulator for nerve cells; their loss results in demyelination. In an effort to counteract the ill effects of radiation, Dr. Tabar’s group first developed a protocol to differentiate human embryonic stem cells (hESCs) into OPCs, then transplanted the OPCs into the brains of irradiated rats. Irradiation of rats with a clinically-relevant dosage results in defects in cognition, memory and motor function.  Injections of the hESC-derived OPCs into the cerebrum in the forebrain, restored cognitive and memory functions. Further testing showed injections of OPCs into the cerebellum, part of the hindbrain, restored motor control.  Histological analysis of post-mortem rat brains showed significant restoration of myelin. Importantly, the differentiation protocol worked with an independent hESC line, as well as with two human induced pluripotent stem cell lines, which can be derived from adults tissues including blood samples. Finally, the differentiation protocol can be made fully Good Manufacturing Practice (GMP)-compliant, a requisite for future use in human patients.There were no tumors or graft overgrowth noted in any of the transplanted animals. This research was supported by a NYSTEM research award, C024413, to Dr. Tabar.

Piao J, Major T, Auyeung G, Policarpio E, Menon J, Droms L, Gutin P, Uryu K, Tchieu J, Soulet D, Tabar V. Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Remyelinate the Brain and Rescue Behavioral Deficits following Radiation. Cell Stem Cell. 2015 Feb 5;16(2):198-210.