京都府立医科大学大学院医学研究科  免疫学(松田研究室)
Department of Immunology, Kyoto Prefectural University of Medicine

プロジェクトのご紹介 7    - Project 7 -

シュワン細胞のダイレクト・リプログラミングと末梢神経損傷の再生
Direct reprogramming of functional Schwann cells that promote regeneration of peripheral nerve

シュワン細胞のダイレクト・リプログラミングと末梢神経損傷の再生

Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system.Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. (Sowa et al, Stem Cells Transl Med.).

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