Revilla Ana, González Clara, Iriondo Amaia, Fernández Bárbara, Prieto Cristina, Marín Carlos, Liste Isabel
Unidad de Regeneración Neural, Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.
J Tissue Eng Regen Med. 2016 Nov;10(11):893-907. doi: 10.1002/term.2021. Epub 2015 Mar 11.
Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd.
在过去几年中，从人类体细胞生成诱导多能干细胞（iPSC）已被证明是再生医学中最具潜在应用价值的发现之一。iPSC正成为研究不同疾病病理学和进行药物筛选的宝贵工具。然而，仍有一些限制因素影响着将基于iPSC的技术应用于治疗前景的可能性。大多数生成iPSC的策略基于通过逆转录病毒或慢病毒载体进行基因传递，这些载体可整合到宿主细胞基因组中，带来插入诱变和致癌转化的显著风险。为避免此类风险，非整合重编程策略已取得重大进展。另一方面，尽管已使用多种不同类型的体细胞来生成iPSC，但对于理想的重编程细胞类型仍未达成共识。在本综述中，我们介绍了人类iPSC生成方面的最新进展，从安全性和效率角度讨论了它们的优势和局限性。我们还介绍了一系列体细胞来源，考虑了它们的重编程能力和组织可及性。从转化医学的角度来看，这两个主题将为阐明在每种基于人类iPSC的治疗中应用的最合适的重编程策略和细胞来源组合提供依据。这项技术能够治疗的多种疾病为再生医学开启了充满希望的未来。版权所有© 2015约翰·威利父子有限公司。
