Non Cell-Autonomous Reprogramming of Adult Ocular Progenitors: Generation of Pluripotent Stem Cells Without Exogenous Transcription Factors
Non Cell-Autonomous Reprogramming of Adult Ocular Progenitors: Generation of Pluripotent Stem Cells Without Exogenous Transcription Factors
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DOI：
10.1002/stem.242
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发表时间：
2009-12-01
期刊：
影响因子：
5.2
通讯作者：
Ahmad, Iqbal
中科院分区：
文献类型：
--
作者：
Balasubramanian, Sudha;Babai, Norbert;Ahmad, Iqbal
通过特异转录因子（TFs）的异位表达，将分化细胞直接重编程为诱导多能干细胞（iPS）细胞，是干细胞在再生医学中应用的重大突破（Takahashi and Yamanaka Cell 2006;126:663-676）。然而，病毒介导的外源性转录因子的表达可能是潜在的有害的，因此，代表了临床使用iPS细胞的障碍。有几种方法，从质粒介导的TF表达到引入重组TF （Yamanaka Cell 2009;137:13-17; Zhou, Wu， Joo等）。Cell Stem Cell 2009；4:31 81-384)，已被报道用于解决与病毒整合相关的风险。我们描述了一种完全通过招募内源基因而不引入遗传物质或外源因素来重编程体细胞祖细胞的替代策略。为此，我们通过微环境诱导内源性iPS细胞基因，重新编程了成年大鼠眼缘上皮的可接近和可再生祖细胞。非细胞自主重编程产生的细胞是多能的，能够分化为功能性神经元、心肌细胞和肝细胞，这可能有助于自体细胞治疗退行性疾病。干细胞2009；27:3053 - 3060
Direct reprogramming of differentiated cells to induced pluripotent stem (iPS) cells by ectopic expression of defined transcription factors (TFs) represents a significant breakthrough towards the use of stem cells in regenerative medicine (Takahashi and Yamanaka Cell 2006;126:663-676). However, the virus-mediated expression of exogenous transcription factors could be potentially harmful and, therefore, represents a barrier to the clinical use of iPS cells. Several approaches, ranging from plasmid-mediated TF expression to introduction of recombinant TFs (Yamanaka Cell 2009;137:13-17; Zhou, Wu, Joo et al. Cell Stem Cell 2009;4:381-384), have been reported to address the risk associated with viral integration. We describe an alternative strategy of reprogramming somatic progenitors entirely through the recruitment of endogenous genes without the introduction of genetic materials or exogenous factors. To this end, we reprogrammed accessible and renewable progenitors from the limbal epithelium of adult rat eye by microenvironment-based induction of endogenous iPS cell genes. Non cell-autonomous reprogramming generates cells that are pluripotent and capable of differentiating into functional neurons, cardiomyocytes, and hepatocytes, which may facilitate autologous cell therapy to treat degenerative diseases. STEM CELLS 2009;27:3053-3060