Lewandowski Jarosław, Kurpisz Maciej
Department of Reproductive Biology and Stem Cells, Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
Arch Immunol Ther Exp (Warsz). 2016 Oct;64(5):349-70. doi: 10.1007/s00005-016-0385-y. Epub 2016 Mar 3.
Developing procedures for the derivation of human pluripotent stem cells (PSCs) gave rise to novel pathways into regenerative medicine research. For many years, stem cells have attracted attention as a potentially unlimited cell source for cellular therapy in neurodegenerative disorders, cardiovascular diseases, and spinal cord injuries, for example. In these studies, adult stem cells were insufficient; therefore, many attempts were made to obtain PSCs by other means. This review discusses key issues concerning the techniques of pluripotent cell acquisition. Technical and ethical issues hindered the medical use of somatic cell nuclear transfer and embryonic stem cells. Therefore, induced PSCs (iPSCs) emerged as a powerful technique with great potential for clinical applications, patient-specific disease modelling and pharmaceutical studies. The replacement of viral vectors or the administration of analogous proteins or chemical compounds during cell reprogramming are modifications designed to reduce tumorigenesis risk and to augment the procedure efficiency. Intensified analysis of new PSC lines revealed other barriers to overcome, such as epigenetic memory, disparity between human and mouse pluripotency, and variable response to differentiation of some iPSC lines. Thus, multidimensional verification must be conducted to fulfil strict clinical-grade requirements. Nevertheless, the first clinical trials in patients with spinal cord injury and macular dystrophy were recently carried out with differentiated iPSCs, encouraging alternative strategies for potential autologous cellular therapies.
人类多能干细胞（PSC）诱导程序的开发为再生医学研究开辟了新途径。多年来，干细胞作为神经退行性疾病、心血管疾病和脊髓损伤等细胞治疗中潜在的无限细胞来源备受关注。例如，在这些研究中，成体干细胞并不充足；因此，人们尝试通过其他方法获取PSC。本综述讨论了多能细胞获取技术的关键问题。技术和伦理问题阻碍了体细胞核移植和胚胎干细胞在医学上的应用。因此，诱导多能干细胞（iPSC）作为一种具有巨大临床应用潜力、可用于患者特异性疾病建模和药物研究的强大技术应运而生。在细胞重编程过程中替换病毒载体或施用类似蛋白质或化合物是旨在降低肿瘤发生风险和提高程序效率的改进措施。对新的PSC系进行深入分析揭示了其他需要克服的障碍，如表观遗传记忆、人类与小鼠多能性的差异以及一些iPSC系对分化的不同反应。因此，必须进行多维度验证以满足严格的临床级要求。尽管如此，最近已对脊髓损伤和黄斑营养不良患者开展了首批使用分化iPSC的临床试验，这为潜在的自体细胞治疗提供了鼓舞人心的替代策略。
