Department of Cardiology, Keio University School of Medicine, Japan.
J Pharmacol Sci. 2014;125(1):1-5. doi: 10.1254/jphs.14r01cp. Epub 2014 Apr 16.
Induced pluripotent stem cell (iPSC) generation is an epoch-making technology. The potential applications for iPSCs are wide-ranging from in vitro disease models to drug discovery. For regenerative medicine in particular, the technology provides great hope for patients with incurable diseases or potentially fatal disorders such as heart failure (HF). However, the true realization of that promise for HF remains uncertain and moving toward the clinical application of iPSCs needs to be stepwise and careful. The establishment of "safe" iPSCs must be a major premise, while genome integration-free and oncogene-free reprogramming is also necessary. Teratoma formation also remains a risk with undifferentiated iPSCs, but it must not happen in patients' bodies. Thus, regardless of the target organ, the differentiated cells from iPSCs must be purified to exclude any possibility of tumorigenicity. The transplantation strategies used for iPSC-derived cells are very important for the recovery of lost cardiac function. Longer engraftment of transplanted iPSCs-derived cardiomyocytes is essential particularly because their survival could be hampered by ischemia, inflammation, apoptosis, immunological rejection, and other cardiac phenomena. Providing these multistep solutions will open the new frontier of regenerative therapies with iPSCs for patients with severe HF.
诱导多能干细胞(iPSC)的产生是一项具有划时代意义的技术。iPSC 的潜在应用范围广泛,从体外疾病模型到药物发现。特别是对于再生医学,该技术为患有无法治愈的疾病或潜在致命疾病(如心力衰竭(HF))的患者提供了巨大的希望。然而,HF 真正实现这一承诺的前景仍不确定,iPSC 的临床应用需要逐步和谨慎地推进。建立“安全”的 iPSC 必须是一个主要前提,同时也需要无基因组整合和无癌基因的重编程。未分化的 iPSC 形成畸胎瘤仍然是一种风险,但绝不能在患者体内发生。因此,无论目标器官如何,都必须从 iPSC 中纯化分化细胞,以排除任何致瘤性的可能性。用于 iPSC 衍生细胞的移植策略对于恢复丧失的心脏功能非常重要。更长时间的移植 iPSC 衍生的心肌细胞的植入是必不可少的,特别是因为它们的存活可能会受到缺血、炎症、细胞凋亡、免疫排斥和其他心脏现象的阻碍。提供这些多步骤的解决方案将为严重 HF 患者的再生治疗开辟新的前沿。