Progress in Process Development and Quality Assessment of Human Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells
LIANG Zuanji1, PANG Peizhuo2, WANG Xiaofang1, QU Shaogang3, MEN Zengxuan1, XU Ren-He2*
MSCs (mesenchymal stem/stromal cells) are present in nearly all tissues and organs of the body.They can be isolated from diverse somatic sources, expanded in vitro, and function primarily by modulating immunity and promoting regeneration through paracrine signaling and small extracellular vesicles, rather than by their stemness. As a form of cell-based therapy, MSCs have been extensively investigated in animal studies and clinical trials for the treatment of a wide range of autoimmune, inflammatory, degenerative diseases, as well as tissue injuries. MSCs have been proposed to be redefined as “medicinal signaling cells”, reflecting their primary mechanism of action through paracrine signaling and immunomodulation. Notably, the Center of Drug Evaluation, NMPA (National Medical Products Administration) has recently proposed adopting the simplified nomenclature “mesenchymal cells”. MSCs can also be continuously derived from PSCs (pluripotent stem cells), which possess unlimited proliferative and differentiation capacities, such as human ESCs (embryonic stem cells) and iPSCs (induced pluripotent stem cells). iPSCs, generated through the epigenetic reprogramming of somatic cells, enable the production of autologous MSCs. In contrast, ESCs exhibit bona fide pluripotency and are free from the need for genetic manipulation or induced reprogramming, thereby avoiding the residual somatic epigenetic memory possibly present in reprogrammed cells. Based on existing literatures, this article provides a comprehensive overview of the differentiation pathways from PSCs to MSCs and the quality evaluation system for the derived MSCs. It focuses on elucidating the research progress of ESC-MSCs (ESCderived MSCs), while also covering the characteristics of iPSC-MSCs (iPSC-derived MSCs). The objective is to provide guidance for the standardized development and clinical translation of PSC-derived MSCs.
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