Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination

Su Wang, Janna Bates, Xiaojie Li, Steven Schanz, Devin Chandler-Militello, Corri Levine, Nimet Maherali, Lorenz Studer, Konrad Hochedlinger, Martha Windrem, Steven A. Goldman

Research output: Contribution to journalArticlepeer-review

462 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)252-264
Number of pages13
JournalCell Stem Cell
Volume12
Issue number2
DOIs
StatePublished - Feb 7 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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