Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination.
Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination.
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DOI：
10.1016/j.stem.2012.12.002
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发表时间：
2013-02-07
期刊：
影响因子：
23.9
通讯作者：
Goldman, Steven A.
中科院分区：
文献类型：
--
作者：
Wang, Su;Bates, Janna;Li, Xiaojie;Schanz, Steven;Chandler-Militello, Devin;Levine, Corri;Maherali, Nimet;Studer, Lorenz;Hochedlinger, Konrad;Windrem, Martha;Goldman, Steven A.
由少突胶质细胞前体细胞(OPC)植入的新生儿可以使先天性髓鞘发育不良的大脑髓鞘形成。为了建立这些细胞的潜在自体来源，我们开发了一种将人诱导多潜能干细胞(HiPSCs)分化为OPC的策略。从3个HIPSC系以及人胚胎干细胞(HESCs)中，我们获得了高度浓缩的OLIG2+/PDGFRα+/NKX2.2+/SOX10+hOPC，并可通过荧光激活细胞分选进一步纯化。HIPSC OPC在体外和体内均能有效地分化为髓鞘少突胶质细胞和星形胶质细胞。新生植入的HiPSC OPC有力地使髓鞘缺陷颤抖小鼠的大脑髓鞘形成，并显著提高了这些小鼠的存活率。HiPSC OPC的髓鞘形成速度和效率高于之前观察到的胎儿组织来源的OPC，并且在移植后9个月内没有发现来自这些移植物的肿瘤。这些结果表明，hPSC来源的OPC在治疗髓鞘丢失的疾病中具有实用价值。
Neonatal engraftment by oligodendrocyte progenitor cells (OPCs) permits the myelination of congenitally dysmyelinated brain. To establish a potential autologous source of these cells, we developed a strategy by which to differentiate human induced pluripotential stem cells (hiPSCs) into OPCs. From 3 hiPSC lines, as well as from human embryonic stem cells (hESCs), we generated highly enriched OLIG2+/PDGFRα+/NKX2.2+/SOX10+ hOPCs, 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 the survival of these mice. 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 utility of hiPSC-derived OPCs in treating disorders of myelin loss.
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DOI：
10.1196/annals.1444.014
发表时间：
2008-01-01
期刊：
YEAR IN NEUROLOGY 2008
影响因子：
--
作者：
Ben-Hur, Tamir;Goldman, Steven A.
通讯作者：
Goldman, Steven A.
影响因子：
16.2
作者：
Zhou, Q;Wang, SL;Anderson, DJ
通讯作者：
Anderson, DJ
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
56.9
作者：
Thomson, JA;Itskovitz-Eldor, J;Jones, JM
通讯作者：
Jones, JM