Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors.
Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors.
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人类诱导多能干细胞的脊髓损伤的早期干预。
DOI：
10.1371/journal.pone.0116933
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kerr CL
中科院分区：
文献类型：
--
作者：
All AH;Gharibani P;Gupta S;Bazley FA;Pashai N;Chou BK;Shah S;Resar LM;Cheng L;Gearhart JD;Kerr CL
诱导多能干细胞（iPS）是再生医学研究的前沿，被设想为个性化组织修复和细胞替代疗法的来源。在这里，我们首次证明，少突胶质细胞祖细胞（OP）可以来自iPS细胞产生的附加体，非整合质粒的方法或标准整合的逆转录病毒，生存和分化成成熟的少突胶质细胞后，早期移植到受伤的脊髓。在所有3个测试的细胞系中，OP分化的效率范围为总细胞的40%至60%，与来自人胚胎干细胞的那些相当。使用附加型载体或逆转录病毒衍生的iPS细胞系产生了相似数量的早期神经祖细胞和神经胶质祖细胞，而附加型质粒衍生的iPS细胞系产生了更多表达晚期标志物O 1和RIP的OP。此外，我们发现，iPS衍生的OP（iPS-OP）移植后24小时中度挫伤性脊髓损伤（SCI）大鼠存活约两个月，超过70%的移植细胞分化成成熟的少突胶质细胞表达髓鞘相关蛋白。移植OP导致在损伤后24小时接受移植的动物中有髓轴突的数量显著增加。此外，与注射热灭活iPS-OP的对照组相比，在iPS处理组中观察到腔大小减少近5倍和神经胶质瘢痕减少。虽然需要进一步的研究来了解所涉及的机制，但这些结果提供了证据，表明患者特异性的iPS衍生的OP可以在急性移植到SCI后存活三个月并改善行为评估（BBB）。这是重要的，因为确定SCI后干细胞注射的时间可能会影响它们的存活和分化能力。
Induced pluripotent stem (iPS) cells are at the forefront of research in regenerative medicine and are envisaged as a source for personalized tissue repair and cell replacement therapy. Here, we demonstrate for the first time that oligodendrocyte progenitors (OPs) can be derived from iPS cells generated using either an episomal, non-integrating plasmid approach or standard integrating retroviruses that survive and differentiate into mature oligodendrocytes after early transplantation into the injured spinal cord. The efficiency of OP differentiation in all 3 lines tested ranged from 40% to 60% of total cells, comparable to those derived from human embryonic stem cells. iPS cell lines derived using episomal vectors or retroviruses generated a similar number of early neural progenitors and glial progenitors while the episomal plasmid-derived iPS line generated more OPs expressing late markers O1 and RIP. Moreover, we discovered that iPS-derived OPs (iPS-OPs) engrafted 24 hours following a moderate contusive spinal cord injury (SCI) in rats survived for approximately two months and that more than 70% of the transplanted cells differentiated into mature oligodendrocytes that expressed myelin associated proteins. Transplanted OPs resulted in a significant increase in the number of myelinated axons in animals that received a transplantation 24 h after injury. In addition, nearly a 5-fold reduction in cavity size and reduced glial scarring was seen in iPS-treated groups compared to the control group, which was injected with heat-killed iPS-OPs. Although further investigation is needed to understand the mechanisms involved, these results provide evidence that patient-specific, iPS-derived OPs can survive for three months and improve behavioral assessment (BBB) after acute transplantation into SCI. This is significant as determining the time in which stem cells are injected after SCI may influence their survival and differentiation capacity.
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影响因子：
5.3
作者：
GEORGE, R;GRIFFIN, JW
通讯作者：
GRIFFIN, JW
影响因子：
4.2
作者：
Dasari, Venkata Ramesh;Spomar, Daniel G.;Dinh, Dzung H.
通讯作者：
Dinh, Dzung H.
影响因子：
2.8
作者：
Bazley, Faith A.;Hu, Charles;All, Angelo H.
通讯作者：
All, Angelo H.
诱导多能干细胞作为加速患者和疾病特异性药物发现的模型。
影响因子：
4.1
作者：
Gunaseeli I;Doss MX;Antzelevitch C;Hescheler J;Sachinidis A
通讯作者：
Sachinidis A
影响因子：
14.5
作者：
Fleming, Jennifer C.;Norenberg, Michael D.;Weaver, Lynne C.
通讯作者：
Weaver, Lynne C.