Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity.
Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity.
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DOI：
10.1371/journal.pone.0052787
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Okano H
中科院分区：
文献类型：
--
作者：
Kobayashi Y;Okada Y;Itakura G;Iwai H;Nishimura S;Yasuda A;Nori S;Hikishima K;Konomi T;Fujiyoshi K;Tsuji O;Toyama Y;Yamanaka S;Nakamura M;Okano H
鼠和人iPSC-NS/PC（诱导多能干细胞衍生的神经干/祖细胞）在移植到啮齿动物的损伤脊髓中后促进功能恢复。然而，对于临床适用性，获得关于移植的人iPSC-NS/PC（hiPSC-NS/PC）用于在非人灵长类动物模型中修复脊髓损伤（SCI）的功效的概念的证据是至关重要的。本研究使用预先评估的“安全”hiPSC-NS/PC克隆和挫伤性SCI的成年普通绒猴（Callithrix jacchus）模型。在第五颈椎节段（C5）诱导SCI，然后在损伤后9天移植hiPSC-NS/PC。行为分析从最初的伤害时间，直到SCI后12周进行。移植的hiPSC-NS/PC存活并分化成所有三种神经谱系。此外，与载体对照动物相比，hiPSC-NS/PC移植增强了轴突保留/再生和血管生成，并防止了SCI后的脱髓鞘。值得注意的是，在移植后至少12周内没有肿瘤形成。定量RT-PCR结果显示，hiPSC-NS/PCs中人神经营养因子mRNA的表达水平明显高于人皮肤成纤维细胞（hDFs）。最后，行为测试表明，hiPSC-NS/PC促进普通绒猴SCI后的功能恢复。总之，这些结果表明，预先评估的安全hiPSC-NS/PC是临床治疗SCI的潜在细胞来源。
Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated “safe” hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI. SCI was induced at the fifth cervical level (C5), followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs). Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.
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影响因子：
20.3
作者：
Hu, Kejin;Yu, Junying;Slukvin, Igor I.
通讯作者：
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通讯作者：
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