Researchers at Case Western Reserve School of Medicine have discovered a technique that directly converts skin cells to the type of brain cells destroyed in patients with multiple sclerosis (MS), cerebral palsy (CP), and other so-called myelin disorders. This discovery was published online on April 14, 2013 in Nature Biotechnology. This breakthrough now enables "on demand" production of myelinating cells, which provide a vital sheath of insulation that protects neurons and enables the delivery of brain impulses to the rest of the body. In patients with MS, CP, and rare genetic disorders called leukodystrophies, myelinating cells are destroyed and cannot be replaced. The new technique involves directly converting fibroblasts - an abundant structural cell present in the skin and most organs - into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain. "Its 'cellular alchemy,'" explained Paul Tesar, Ph.D., assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine and senior author of the study. "We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy." In a process termed "cellular reprogramming," researchers manipulated the levels of three naturally occurring transcription factors to induce fibroblast cells to become precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs). Dr. Tesar's team, led by Case Western Reserve researchers and co-first authors Dr. Fadi Najm and Dr. Angela Lager, rapidly generated billions of these induced OPCs (called iOPCs). Even more important, they showed that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice—a result that offers hope the technique might be used to treat human myelin disorders.
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