Rapid induction and long-term self-renewal of neural crest-derived ectodermal chondrogenic cells from hPSCs

Pei Shen; Lu Chen; Dahe Zhang; Simo Xia; Zhuman Lv; Duohong Zou; Zhiyuan Zhang; Chi Yang; Wenlin Li

doi:10.1038/s41536-022-00265-0

Rapid induction and long-term self-renewal of neural crest-derived ectodermal chondrogenic cells from hPSCs

NPJ Regen Med. 2022 Dec 8;7(1):69. doi: 10.1038/s41536-022-00265-0.

Authors

Pei Shen^#¹, Lu Chen^#¹, Dahe Zhang¹, Simo Xia¹, Zhuman Lv², Duohong Zou¹, Zhiyuan Zhang¹, Chi Yang³, Wenlin Li⁴

Affiliations

¹ Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China.
² Department of Cell Biology, Naval Medical University, 200433, Shanghai, China.
³ Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China. yangchi63@hotmail.com.
⁴ Department of Cell Biology, Naval Medical University, 200433, Shanghai, China. liwenlin@smmu.edu.cn.

^# Contributed equally.

Abstract

Articular cartilage is highly specific and has limited capacity for regeneration if damaged. Human pluripotent stem cells (hPSCs) have the potential to generate any cell type in the body. Here, we report the dual-phase induction of ectodermal chondrogenic cells (ECCs) from hPSCs through the neural crest (NC). ECCs were able to self-renew long-term (over numerous passages) in a cocktail of growth factors and small molecules. The cells stably expressed cranial neural crest-derived mandibular condylar cartilage markers, such as MSX1, FOXC1 and FOXC2. Compared with chondroprogenitors from iPSCs via the paraxial mesoderm, ECCs had single-cell transcriptome profiles similar to condylar chondrocytes. After the removal of the cocktail sustaining self-renewal, the cells stopped proliferating and differentiated into a homogenous chondrocyte population. Remarkably, after transplantation, this cell lineage was able to form cartilage-like structures resembling mandibular condylar cartilage in vivo. This finding provides a framework to generate self-renewing cranial chondrogenic progenitors, which could be useful for developing cell-based therapy for cranial cartilage injury.