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Induced pluripotent stem cells:from Nobel Prizes to clinical applications

机译:诱导多能干细胞:从诺贝尔奖到临床应用

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摘要

Advances in basic hepatology have been constrained for many years by the inability to culture primary hepatocytes in vitro, until just over five years ago when the scientific playing field was changed beyond recognition with the demonstration that human skin fibroblasts could be reprogrammed to resemble embryonic cells. The reprogrammed cells, known as induced pluripotent stem cells (iPSCs), were then shown to have the capacity to re-differentiate into almost any human cell type, including hepatocytes. The unlimited number and isogenic nature of the cells that can be generated from tiny fragments of tissue have massive implications for the study of human liver diseases in vitro. Of more immediate clinical importance were recent data demonstrating precision gene therapy on patient specific iPSCs, which opens up the real and exciting possibility of autologous hepatocyte transplantation as a substitute for allogeneic whole liver transplantation, which has been an effective approach to end-stage liver disease, but one that has now been outstripped by demand. In this review, we describe the historical development, current technology and potential clinical applications of induced pluripotency, concluding with a perspective on possible future directions in this dynamic field.
机译:由于无法在体外培养原代肝细胞,多年来一直限制着基本肝病学的发展,直到五年多前,科学领域才发生了变化,人们证明人类皮肤的成纤维细胞可以重编程为类似于胚胎细胞,这一事实已使人们认识不到。重新编程的细胞被称为诱导多能干细胞(iPSC),然后被证明具有重新分化为几乎所有人类细胞类型(包括肝细胞)的能力。由组织的细小片段产生的细胞的无限数量和等基因性质对体外人类肝脏疾病的研究具有重大意义。具有更近期临床意义的是最近的数据,该数据证明了对患者特异性iPSC进行精确基因治疗的可能性,这为自体肝细胞移植替代同种异体全肝移植开辟了真正令人兴奋的可能性,这已成为治疗晚期肝病的有效方法,但现在已被需求所超越。在这篇综述中,我们描述了诱导多能性的历史发展,当前技术和潜在的临床应用,并对这一动态领域的未来可能发展方向进行了展望。

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