Development of histocompatible primate-induced pluripotent stem cells for neural transplantation.
Development of histocompatible primate-induced pluripotent stem cells for neural transplantation.
复制标题
DOI：
10.1002/stem.662
复制
发表时间：
2011-07
期刊：
影响因子：
5.2
通讯作者：
Isacson, Ole
中科院分区：
文献类型：
--
作者：
Deleidi, Michela;Hargus, Gunnar;Hallett, Penelope;Osborn, Teresia;Isacson, Ole
免疫排斥和肿瘤形成的风险可能是干细胞移植领域最大的障碍。在这里，我们报道了从食蟹猴（CM）皮肤成纤维细胞中产生的几种诱导多能干细胞（iPSCs），这些细胞携带特定的主要组织相容性复合体（MHC）单倍型。为了收集MHC匹配的iPSCs，我们采用微卫星PCR分析对25 CM的MHC位点进行了基因分型。利用逆转录病毒感染真皮皮肤成纤维细胞，我们产生了几种携带不同单倍型的CM-iPSC系。我们表征了CM-iPSCs的免疫学特性，并证明CM-iPSCs可以在体外诱导沿特定神经元群（如中脑多巴胺能（DA）神经元）分化。CM-iPSCs生成的中脑样DA神经元整合到帕金森病（PD）啮齿动物模型的纹状体中并促进行为恢复。重要的是，移植动物在移植后6个月未观察到肿瘤形成或炎症反应。我们相信，这种组织相容性iPSCs的产生和表征将允许iPSCs在再生医学领域用于神经退行性疾病和其他几种人类疾病的安全性和有效性的临床前验证。
Immune rejection and risk of tumor formation are perhaps the greatest hurdles in the field of stem cell transplantation. Here, we report the generation of several lines of induced pluripotent stem cells (iPSCs) from Cynomolgus macaque (CM) skin fibroblasts carrying specific major histocompatibility complex (MHC) haplotypes. In order to develop a collection of MHC-matched iPSCs, we genotyped the MHC locus of 25 CM by microsatellite PCR analysis. Using retroviral infection of dermal skin fibroblasts, we generated several CM-iPSC lines carrying different haplotypes. We characterized the immunological properties of CM-iPSCs and demonstrated that CM-iPSCs can be induced to differentiate in vitro along specific neuronal populations, such as midbrain dopaminergic (DA) neurons. Midbrain-like DA neurons generated from CM-iPSCs integrated into the striatum of a rodent model of Parkinson’s disease (PD) and promoted behavioral recovery. Importantly, neither tumor formation nor inflammatory reactions were observed in the transplanted animals up to six months after transplantation. We believe that the generation and characterization of such histocompatible iPSCs will allow the pre-clinical validation of safety and efficacy of iPSCs for neurodegenerative diseases and several other human conditions in the field of regenerative medicine.
登录
查看更多内容
影响因子：
64.5
作者：
Park IH;Arora N;Huo H;Maherali N;Ahfeldt T;Shimamura A;Lensch MW;Cowan C;Hochedlinger K;Daley GQ
通讯作者：
Daley GQ
DOI：
10.1007/bf03206631
发表时间：
2004-10-01
期刊：
NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Barker, Roger A;Widner, Hakan
通讯作者：
Widner, Hakan
影响因子：
14.5
作者：
Mendez, I;Sanchez-Pernaute, R;Isacson, O
通讯作者：
Isacson, O
影响因子：
64.5
作者：
LIU, J;FARMER, JD;SCHREIBER, SL
通讯作者：
SCHREIBER, SL
影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.