Jin Wei, He Yi, Li Tuo, Long Fei, Qin Xin, Yuan Yuan, Gao Ge, Shakhawat Hosen Md, Liu Xinguang, Jin Guoxiang, Zhou Zhongjun
School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Chinese Academy of Sciences Regenerative Medicine of Hong Kong, Hong Kong, China.
Cell Biosci. 2022 Mar 15;12(1):31. doi: 10.1186/s13578-022-00753-2.
Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages. The infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Despite their great potential in therapeutic applications, several drawbacks have hindered its clinical translation, including limited number of replication, compromised potential and altered function in late passages. The aim of this study is to establish an efficient method for the production of MSCs from pluripotent stem cells for potential clinical application in rare human disease Hutchinson-Gilford progeria syndrome.
We established a robust method allowing rapid derivation of MSCs from both human iPSCs and ESCs via a temporal induction of neural ectoderm in chemically defined media. The iPSC- and ESC-derived MSCs satisfy the standard criteria of surface markers. They exhibited a high tri-lineage differentiation potential with over 90% transcriptional similarity to the primary MSCs derived from bone marrow. To evaluate the potential application of this method in disease modeling, MSCs were generated from iPSCs derived from a patient with Hutchinson-Gilford progeria syndrome (HGPS-MSCs) and from mutation-rectified HGPS-iPSCs (cHGPS-MSCs). HGPS-MSCs manifested accelerated senescence whereas mutation rectification rescued cellular senescence in HGPS-MSCs.
The robust method of MSC derivation from ESCs and iPSCs provides an efficient approach to rapidly generate sufficient MSCs for in vitro disease modeling and clinical applications.
间充质干细胞（MSCs）因其能够分化为多种细胞谱系而成为再生医学的中流砥柱。人类多能干细胞（PSCs）的无限增殖潜力为MSCs提供了无限的来源。尽管它们在治疗应用中具有巨大潜力，但一些缺点阻碍了其临床转化，包括复制数量有限、后期传代时潜能受损和功能改变。本研究的目的是建立一种从多能干细胞高效生产MSCs的方法，用于罕见人类疾病哈钦森 - 吉尔福德早衰综合征的潜在临床应用。
我们建立了一种强大的方法，通过在化学成分明确的培养基中短暂诱导神经外胚层，从人类诱导多能干细胞（iPSCs）和胚胎干细胞（ESCs）快速衍生出MSCs。iPSC和ESC来源的MSCs满足表面标志物的标准标准。它们表现出高的三系分化潜能，与源自骨髓的原代MSCs具有超过90%的转录相似性。为了评估该方法在疾病建模中的潜在应用，从患有哈钦森 - 吉尔福德早衰综合征患者的iPSCs（HGPS - MSCs）和突变纠正的HGPS - iPSCs（cHGPS - MSCs）中生成了MSCs。HGPS - MSCs表现出加速衰老，而突变纠正挽救了HGPS - MSCs中的细胞衰老。
从ESCs和iPSCs衍生MSCs的强大方法为快速生成足够的MSCs用于体外疾病建模和临床应用提供了一种有效途径。
