Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury
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DOI:
10.1523/jneurosci.0311-05.2005
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发表时间:
2005-05-11
影响因子:
5.3
通讯作者:
Steward, O
Steward, O
中科院分区:
医学1区
文献类型:
--
作者:
Keirstead, HS;Nistor, G;Steward, O

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脱髓鞘导致脊髓损伤后的功能丧失,因此潜在的治疗策略涉及替换髓鞘形成细胞。在这里,我们表明,移植人胚胎干细胞(hESC)衍生的少突胶质细胞祖细胞(OPCs)到成年大鼠脊髓损伤增强髓鞘再生,促进改善运动功能。伤后7 d或10个月注射OPCs。在这两种情况下,移植的细胞存活,重新分布在短距离内,并分化成少突胶质细胞。损伤后7天接受OPCs的动物表现出增强的髓鞘再生和显著改善的运动能力。相反,当OPCs在损伤后10个月移植时,没有增强髓鞘再生或运动恢复。这些研究证明了将hESC预分化为功能性OPCs的可行性,并证明了其在脊髓损伤后早期时间点的治疗潜力。
Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin- forming cells. Here, we show that transplantation of human embryonic stem cell ( hESC)- derived oligodendrocyte progenitor cells ( OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.