![]() MSCs can be derived and purified with typical surfaces markers from the spontaneous differentiation of embryonic body (EB), a sphere culture derivatives of hPSCs. ![]() co-cultured hESCs with mouse OP9 cells for 40 days followed by FACS sorting for CD73 + cells to enrich the MSC population. Up till now, various strategies and modified protocols have been developed to generate MSCs from hPSCs. Human pluripotent stem cells (hPSCs), including embryonic stem cells and induced pluripotent stem cells, possess the capacity of indefinite proliferation and differentiation into all three germ layers, making hPSCs an ideal, easily accessible and safe source for large-scale production of high-quality MSCs. On the other hand, although MSCs exhibit low immunogenicity in general, the allogenic MSCs from bone marrow (BM-MSCs) were reported to induce undesired immune response in several animal models. In addition, tissue-derived MSCs suffer from tissue and donor variability, especially with the regard of age and disease-status of the donors, which may explain the discrepancy in the efficacies of preclinical evaluation of MSCs. The quantity of MSCs isolated from primary tissues is far from sufficient for clinical applications and the primary MSCs usually exhibit limited proliferative capacity, altered functionality and compromised differentiation potential over long-term culture. However, there are several drawbacks in MSCs derived from adult tissues. MSCs have been successfully isolated and expanded from multiple human tissues including bone marrow, adipose tissue, umbilical cord, muscle, liver, cartilage, and lung. Therefore, MSCs have emerged as the most frequently used bio-reagent in the fields of regenerative medicine and tissue engineering. In addition, MSCs in culture secrete a myriad of bioactive molecules, including growth factors, cytokines, chemokines, and mRNA/microRNA-containing macrovesicles, which have been successfully used in clinical cosmetology. Both ex vivo and animal studies have shown that MSCs can home to sites of the injuries or inflammation to create a favorable microenvironment to support the survival and functional recovery of injured cells, promoting their proliferation via direct cell–cell contact or paracrine secretion. Because of the low immunogenicity, high regenerative capability and strong immunomodulatory properties, both allogenic and autologous MSCs have been deployed in a large number of phase I-III clinical trials for degenerative diseases and autoimmune disorders, such as ischemic heart diseases, neurodegenerative disorders, graft versus host disease and Crohn’s disease, as well as hematopoietic stem cell (HSC) engraftment failure. MSCs are characterized by their fibroblast-like morphology, high potential of osteogenesis, adipogenesis and chondrogenesis, positive for a panel of typical surface markers, including CD73, CD90 and CD105. Mesenchymal stem cells (MSCs) are multipotent progenitor cells firstly isolated from bone marrow. 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. HGPS-MSCs manifested accelerated senescence whereas mutation rectification rescued cellular senescence in HGPS-MSCs. 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). They exhibited a high tri-lineage differentiation potential with over 90% transcriptional similarity to the primary MSCs derived from bone marrow. The iPSC- and ESC-derived MSCs satisfy the standard criteria of surface markers. 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 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. 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 infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages.
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