Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322, USA.
Protein Cell. 2012 Apr;3(4):271-7. doi: 10.1007/s13238-012-2922-8. Epub 2012 Apr 19.
With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of human patients with defined factors, hold promise for regenerative medicine because they can provide a renewable source of autologous cells for cell therapy without the concern for immune rejection. In addition, iPSCs provide a unique opportunity to model human diseases with complex genetic traits, and a panel of human diseases have been successfully modeled in vitro by patient-specific iPSCs. Despite these progresses, recent studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to the immunogenicity of some cells differentiated from iPSCs. The oncogenic potential of iPSCs is further underscored by the findings that the critical tumor suppressor p53, known as the guardian of the genome, suppresses induced pluripotency. Therefore, the clinic application of iPSCs will require the optimization of the reprogramming technology to minimize the genetic and epigenetic abnormalities associated with induced pluripotency.
诱导多能干细胞(iPSCs)可无限自我更新,并分化为体内所有细胞类型,通过定义因子从人类患者的体细胞中重编程而来,为再生医学带来了希望,因为它们可以提供可再生的自体细胞来源,用于细胞治疗,而不必担心免疫排斥。此外,iPSCs 为模拟具有复杂遗传特征的人类疾病提供了独特的机会,并且已经通过患者特异性 iPSCs 成功地在体外模拟了一系列人类疾病。尽管取得了这些进展,但最近的研究引起了人们对 iPSCs 的遗传和表观遗传异常的关注,这些异常可能导致 iPSCs 分化的一些细胞的免疫原性。iPSCs 的致癌潜能进一步被以下发现所强调:已知作为基因组守护者的关键肿瘤抑制因子 p53 抑制了诱导多能性。因此,iPSCs 的临床应用将需要优化重编程技术,以最大限度地减少与诱导多能性相关的遗传和表观遗传异常。