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By optimizing the Schwann cell induction system, which was originally developed for trans\u2010differentiation of bone marrow mesenchymal stem cells into Schwann cells, we established a system to directly convert adult human skin fibroblasts into cells comparable to authentic human Schwann cells without gene introduction. Serial treatments with beta\u2010mercaptoethanol, retinoic acid, and finally a cocktail of basic fibroblast growth factor, forskolin, platelet\u2010derived growth factor\u2010AA, and heregulin\u2010\u03b21 (EGF domain) converted fibroblasts into cells expressing authentic Schwann cell markers at an efficiency of approximately 75%. Genome\u2010wide gene expression analysis suggested the conversion of fibroblasts into the Schwann cell\u2010lineage. Transplantation of induced Schwann cells into severed peripheral nerve of rats facilitated axonal regeneration and robust functional recovery in sciatic function index comparable to those of authentic human Schwann cells. The contributions of induced Schwann cells to myelination of regenerated axons and re\u2010formation of neuromuscular junctions were also demonstrated. Our data clearly demonstrated that cells comparable to functional Schwann cells feasible for the treatment of neural disease can be induced from adult human skin fibroblasts without gene introduction. This direct conversion system will be beneficial for clinical applications to peripheral and central nervous system injuries and demyelinating diseases.<\/jats:p>","DOI":"10.1002\/glia.23582","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T07:56:00Z","timestamp":1547452560000},"page":"950-966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Direct conversion of adult human skin fibroblasts into functional Schwann cells that achieve robust recovery of the severed peripheral nerve in rats"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-9767","authenticated-orcid":false,"given":"Masaaki","family":"Kitada","sequence":"first","affiliation":[{"name":"Department of Stem Cell Biology and Histology Tohoku University Graduate School of Medicine  Sendai 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