Caudalized human iPSC-derived neural progenitor cells produce neurons and glia but fail to restore function in an early chronic spinal cord injury model.
Caudalized human iPSC-derived neural progenitor cells produce neurons and glia but fail to restore function in an early chronic spinal cord injury model.
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尾部化的人 iPSC 衍生的神经祖细胞产生神经元和神经胶质细胞，但无法恢复早期慢性脊髓损伤模型中的功能。
DOI：
10.1016/j.expneurol.2013.07.010
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发表时间：
2013-10
影响因子：
5.3
通讯作者：
Horner, Philip J.
中科院分区：
文献类型：
--
作者：
Nutt, Samuel E.;Chang, Eun-Ah;Suhr, Steven T.;Schlosser, Laura O.;Mondello, Sarah E.;Moritz, Chet T.;Cibelli, Jose B.;Horner, Philip J.
神经祖细胞（NPCs）在治疗脊髓损伤（SCI）方面显示出适度的潜力和一些副作用（如异常性疼痛）。然而，在少数情况下，npc在慢性阶段表现出了希望。鉴于有127.5万人患有慢性瘫痪，迫切需要严格评估细胞类型和方法，以安全有效地治疗这一毁灭性疾病。我们首次研究了从人类诱导多能干细胞（hiPSCs）中提取的NPCs修复慢性脊髓损伤的临床前潜力。hipsc分化为区域特异性（即尾侧）npc，然后移植到一个新的、临床相关的早期慢性颈椎脊髓损伤模型中。我们建立了成功移植尾化hipsc - npc的条件，并证明了它们在早期慢性损伤环境中整合和产生多种神经谱系的卓越能力。与先前报道的急性和亚急性损伤模型相反，hipsc来源的神经细胞在早期慢性颈椎模型中的存活和整合并未导致前肢功能的显着改善或诱导异常性疼痛。这些数据表明，虽然hipsc显示出希望，但未来的工作需要关注特定的hipsc衍生物或联合疗法，以恢复早期慢性损伤环境中的功能。
Neural progenitor cells (NPCs) have shown modest potential and some side effects (e.g. allodynia) for treatment of spinal cord injury (SCI). In only a few cases, however, have NPCs shown promise at the chronic stage. Given the 1.275 million people living with chronic paralysis, there is a significant need to rigorously evaluate the cell types and methods for safe and efficacious treatment of this devastating condition. For the first time, we examined the pre-clinical potential of NPCs derived from human induced pluripotent stem cells (hiPSCs) to repair chronic SCI. hiPSCs were differentiated into region-specific (i.e. caudal) NPCs, then transplanted into a new, clinically relevant model of early chronic cervical SCI. We established the conditions for successful transplantation of caudalized hiPSC-NPCs and demonstrate their remarkable ability to integrate and produce multiple neural lineages in the early chronic injury environment. In contrast to prior reports in acute and sub-acute injury models, survival and integration of hiPSC-derived neural cells in the early chronic cervical model did not lead to significant improvement in forelimb function or induce allodynia. These data indicate that while hiPSCs show promise, future work needs to focus on the specific hiPSC-derivatives or co-therapies that will restore function in the early chronic injury setting.
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影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
3.4
作者：
Ikegami, T;Nakamura, M;Okano, H
通讯作者：
Okano, H
影响因子：
1.7
作者：
Bass, AH;Baker, R
通讯作者：
Baker, R
DOI：
10.1016/j.jstrokecerebrovasdis.2011.09.008
发表时间：
2013-05
期刊：
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
影响因子：
--
作者：
Jensen MB;Yan H;Krishnaney-Davison R;Al Sawaf A;Zhang SC
通讯作者：
Zhang SC
影响因子：
5.7
作者：
Fehlings, Michael G.;Vawda, Reaz
通讯作者：
Vawda, Reaz