Hypoxic ADSCs-derived EVs promote the proliferation and chondrogenic differentiation of cartilage stem/progenitor cells

Ke Xue; Yongkang Jiang; Xiaodie Zhang; Jun Wu; Lin Qi; Kai Liu

doi:10.1080/21623945.2021.1945210

Hypoxic ADSCs-derived EVs promote the proliferation and chondrogenic differentiation of cartilage stem/progenitor cells

Adipocyte. 2021 Dec;10(1):322-337. doi: 10.1080/21623945.2021.1945210.

Authors

Ke Xue¹, Yongkang Jiang¹, Xiaodie Zhang¹, Jun Wu², Lin Qi³, Kai Liu¹

Affiliations

¹ Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai, PR China.
² Department of Orthopedics, The First People's Hospital of Changzhou, Jiangsu Changzhou, China.
³ Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China.

Abstract

Cartilage tissue engineering is a promising option for repairing cartilage defects, although harvesting a large number of seeding cells remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles (EVs) may play a major role in cell-cell and tissue-tissue communication. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived EVs on CSPCs proliferation and differentiation. The characteristics of ADSCs-derived EVs were identified, and proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. SEM, histological staining, biochemical and biomechanical analysis was performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture. The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40-1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induce CSPCs to produce significantly more cartilage matrix and proteoglycan. In conclusion, hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.

Keywords: Cartilage stem/progenitor cells; cartilage tissue engineering; differentiation; extracellular vesicles; hypoxic adipose-derived stem cells; proliferation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Cartilage*
Cell Differentiation
Cell Proliferation
Extracellular Vesicles*
Stem Cells

Grants and funding

This work was supported by the National Natural Science Foundation of China (81801929) and Major Scientific and Technological Project of Changzhou Municipal Commission of Health and Family Planning (ZD201907).