MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration.

Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1+ mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1+ cells, where a distinct PDGFRAlow subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1+PDGFRAlow limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1+PDGFRAlow LML cells might be a prominent stem cell source for human cartilage regeneration. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Yuansong Liao, Fanchen Kang, Jingfei Xiong, Kun Xie, Mingxu Li, Ling Yu, Yuqing Wang, Hanyi Chen, Guogen Ye, Yike Yin, Weihua Guo, Haoyang Cai, Qing Zhu, Zhonghan Li. MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration. Stem cell reports. 2024 Mar 12;19(3):399-413

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PMID: 38428414

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