Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, People's Republic of China.
Department of Biology, College of Arts and Sciences, University of Hartford, West Hartford, Connecticut, USA.
Stem Cells. 2019 May;37(5):572-581. doi: 10.1002/stem.2964. Epub 2019 Jan 21.
Despite the long discrepancy over their definition, heterogeneity, and functions, mesenchymal stem cells (MSCs) have proved to be a key player in tissue repair and homeostasis. Generally, somatic tissue-derived MSCs (st-MSCs) are subject to quality variations related to donated samples and biosafety concern for transmission of potential pathogens from the donors. In contrast, human pluripotent stem cells (hPSCs) are unlimited in supply, clear in the biological background, and convenient for quality control, genetic modification, and scale-up production. We, and others, have shown that hPSCs can differentiate in two dimensions or three dimensions to MSCs (ps-MSCs) via embryonic (mesoderm and neural crest) or extraembryonic (trophoblast) cell types under serum-containing or xeno-free and defined conditions. Compared to st-MSCs, ps-MSCs appear less mature, proliferate faster, express lower levels of inflammatory cytokines, and respond less to traditional protocols for st-MSC differentiation to other cell types, especially adipocytes. Nevertheless, ps-MSCs are capable of immune modulation and treatment of an increasing number of animal disease models via mitochondria transfer, paracrine, exosomes, and direct differentiation, and can be potentially used as a universal and endless therapy for clinical application. This review summarizes the progress on ps-MSCs and discusses perspectives and challenges for their potential translation to the clinic. Stem Cells 2019;37:572-581.
尽管间充质干细胞（MSCs）在定义、异质性和功能上存在长期分歧，但它们已被证明是组织修复和稳态的关键参与者。通常，源自体组织的 MSCs（st-MSCs）存在与供体样本相关的质量变化以及从供体传播潜在病原体的生物安全问题。相比之下，人类多能干细胞（hPSCs）供应不受限制，生物学背景清晰，便于质量控制、基因修饰和规模化生产。我们和其他人已经表明，hPSCs 可以在含有血清或无动物源和定义条件下通过胚胎（中胚层和神经嵴）或胚胎外（滋养层）细胞类型二维或三维分化为 MSCs（ps-MSCs）。与 st-MSCs 相比，ps-MSCs 似乎不太成熟，增殖更快，表达较低水平的炎症细胞因子，对 st-MSC 向其他细胞类型（特别是脂肪细胞）分化的传统方案反应较小。然而，ps-MSCs 通过线粒体转移、旁分泌、外泌体和直接分化具有免疫调节和治疗越来越多的动物疾病模型的能力，并可作为一种通用且无限的治疗方法潜在地用于临床应用。本综述总结了 ps-MSCs 的进展，并讨论了其潜在转化为临床应用的观点和挑战。干细胞 2019;37:572-581。
