title: Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination.
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.
authors: Center for Translational Neuromedicine and Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors: Su
authors: S
authors: Wang
authors: Janna
authors: J
authors: Bates
authors: Xiaojie
authors: X
authors: Li
authors: Steven
authors: S
authors: Schanz
authors: Devin
authors: D
authors: Chandler-Militello
authors: Corri
authors: C
authors: Levine
authors: Nimet
authors: N
authors: Maherali
authors: Lorenz
authors: L
authors: Studer
authors: Konrad
authors: K
authors: Hochedlinger
authors: Martha
authors: M
authors: Windrem
authors: Steven A
authors: SA
authors: Goldman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002607:Charcot-Marie-Tooth Disease / Q000628:therapy*; D005434:Flow Cytometry; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009687:Nuclear Proteins; D009836:Oligodendroglia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors
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