Rapid and robust derivation of mesenchymal stem cells from human pluripotent stem cells via temporal induction of neuralized ectoderm

通过神经化外胚层的时间诱导,从人类多能干细胞快速、稳健地衍生间充质干细胞

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作者:Wei Jin, Yi He, Tuo Li, Fei Long, Xin Qin, Yuan Yuan, Ge Gao, Hosen Md Shakhawat, Xinguang Liu, Guoxiang Jin, Zhongjun Zhou

Background

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

Conclusions

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.

Results

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. Conclusions: 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.

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