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Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications
Signal Transduction and Targeted Therapy ( IF 39.3 ) Pub Date : 2024-04-26 , DOI: 10.1038/s41392-024-01809-0
Jonas Cerneckis , Hongxia Cai , Yanhong Shi

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable to genetic engineering, and can be differentiated into most somatic cell types. iPSCs have been widely applied to model human development and diseases, perform drug screening, and develop cell therapies. In this review, we outline key developments in the iPSC field and highlight the immense versatility of the iPSC technology for in vitro modeling and therapeutic applications. We begin by discussing the pivotal discoveries that revealed the potential of a somatic cell nucleus for reprogramming and led to successful generation of iPSCs. We consider the molecular mechanisms and dynamics of somatic cell reprogramming as well as the numerous methods available to induce pluripotency. Subsequently, we discuss various iPSC-based cellular models, from mono-cultures of a single cell type to complex three-dimensional organoids, and how these models can be applied to elucidate the mechanisms of human development and diseases. We use examples of neurological disorders, coronavirus disease 2019 (COVID-19), and cancer to highlight the diversity of disease-specific phenotypes that can be modeled using iPSC-derived cells. We also consider how iPSC-derived cellular models can be used in high-throughput drug screening and drug toxicity studies. Finally, we discuss the process of developing autologous and allogeneic iPSC-based cell therapies and their potential to alleviate human diseases.



中文翻译:

诱导多能干细胞(iPSC):诱导和应用的分子机制

诱导多能干细胞 (iPSC) 技术已经改变了体外研究,并为推进再生医学带来了巨大希望。 iPSC 具有几乎无限扩增的能力,适合基因工程,并且可以分化为大多数体细胞类型。 iPSC 已广泛应用于人类发育和疾病模型、药物筛选和细胞疗法开发。在这篇综述中,我们概述了 iPSC 领域的关键发展,并强调了 iPSC 技术在体外建模和治疗应用方面的巨大多功能性。我们首先讨论一些关键发现,这些发现揭示了体细胞核重编程的潜力,并导致 iPSC 的成功生成。我们考虑体细胞重编程的分子机制和动力学以及可用于诱导多能性的多种方法。随后,我们讨论了各种基于 iPSC 的细胞模型,从单一细胞类型的单一培养物到复杂的三维类器官,以及如何应用这些模型来阐明人类发育和疾病的机制。我们使用神经系统疾病、2019 年冠状病毒病 (COVID-19) 和癌症的例子来强调可以使用 iPSC 衍生细胞进行建模的疾病特异性表型的多样性。我们还考虑如何将 iPSC 衍生的细胞模型用于高通量药物筛选和药物毒性研究。最后,我们讨论了开发自体和同种异体 iPSC 细胞疗法的过程及其缓解人类疾病的潜力。

更新日期:2024-04-26
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