Park Junmyeong, Kim Jueun, Shin Borami, Sch Ler Hans R, Kim Johnny, Kim Kee-Pyo
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of General Pediatrics, University of Children's Hospital M?nster, M?nster, Germany.
Int J Stem Cells. 2024 Nov 30;17(4):363-373. doi: 10.15283/ijsc23148. Epub 2024 Jan 29.
Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.
体细胞重编程为多能性是由山中因子Oct4、Sox2、Klf4和c-Myc介导的。由此产生的诱导多能干细胞(iPSC)凭借其分化为不同类型功能细胞的能力,在再生医学领域具有巨大潜力。具体而言,直接从患者体内获得的iPSC为创建疾病模型提供了一个强大的平台。这有助于阐明人类疾病的病理机制,并开发减轻疾病表型的新型治疗药物。此外,通过基因编辑技术进行基因和表型校正的患者来源iPSC或提供特定药物制剂可用于临床前和临床试验,以研究其治疗潜力。尽管在开发重编程方法方面取得了巨大进展,但iPSC生成的效率仍然很低,并且因供体细胞类型而异,这阻碍了iPSC技术的潜在应用。本文回顾了显示导致iPSC生成的重要发现的组织学时间线,并通过强调用于iPSC生成的供体细胞类型来讨论iPSC技术的最新进展。