Cell Stem Cell
Volume 12, Issue 2, 7 February 2013, Pages 252-264
Journal home page for Cell Stem Cell

Clinical Progress
Human iPSC-Derived Oligodendrocyte Progenitor Cells Can Myelinate and Rescue a Mouse Model of Congenital Hypomyelination

https://doi.org/10.1016/j.stem.2012.12.002Get rights and content
Under an Elsevier user license
open archive

Summary

Neonatal engraftment by oligodendrocyte progenitor cells (OPCs) permits the myelination of the congenitally dysmyelinated brain. To establish a potential autologous source of these cells, we developed a strategy by which to differentiate human induced pluripotent stem cells (hiPSCs) into OPCs. From three hiPSC lines, as well as from human embryonic stem cells (hESCs), we generated highly enriched OLIG2+/PDGFRα+/NKX2.2+/SOX10+ human OPCs, which could be further purified using fluorescence-activated cell sorting. hiPSC OPCs efficiently differentiated into both myelinogenic oligodendrocytes and astrocytes, in vitro and in vivo. Neonatally engrafted hiPSC OPCs robustly myelinated the brains of myelin-deficient shiverer mice and substantially increased their survival. The speed and efficiency of myelination by hiPSC OPCs was higher than that previously observed using fetal-tissue-derived OPCs, and no tumors from these grafts were noted as long as 9 months after transplant. These results suggest the potential utility of hiPSC-derived OPCs in treating disorders of myelin loss.

Highlights

► Myelinating oligodendrocyte progenitor cells (OPCs) were generated from human iPSCs ► hiPSC OPCs myelinated the brains of shiverer mice and increased their survival ► Myelination by hiPSC OPCs was faster than that of fetal-tissue-derived OPCs ► hiPSC OPCs produced both astrocytes and oligodendrocytes and were not tumorigenic

Cited by (0)