Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury

摘要

class="head no_bottom_margin" id="sec1title">IntroductionPrevious studies describing functional recovery following transplantation of neural stem/progenitor cells (NS/PCs) in spinal cord injury (SCI) models demonstrated the therapeutic promise of this approach (, ). A number of putative underlying mechanisms have been suggested, including cell replacement by grafted NS/PC-derived neurons, astrocytes, and oligodendrocytes; trophic support for increased survival of the host neural cells and host-mediated repair processes; and, more recently, axonal remyelination by grafted NS/PC-derived oligodendrocytes (, , , ). Human NS/PCs and human-induced pluripotent stem cell-derived NS/PCs (hiPSC-NS/PCs) predominantly differentiate into neurons, and, to a lesser extent, into mature oligodendrocytes both in vitro and in vivo (, , , ). We therefore developed a protocol for the induction of oligodendroglial differentiation of hiPSC-NS/PCs in vitro (). In the present study, we used a pre-evaluated safe line of induced pluripotent stem cells (iPSCs; 201B7) (, ) and induced their differentiation into oligodendrocyte precursor cell-enriched NS/PCs (hiPSC-OPC-enriched NS/PCs). The aim of this study was to evaluate the therapeutic potential of hiPSC-OPC-enriched NS/PCs in the treatment of SCI.