Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

Yu Xia; Xiao-Tao He; Xin-Yue Xu; Bei-Min Tian; Ying An; Fa-Ming Chen

doi:10.7717/peerj.8970

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

PeerJ. 2020 Apr 24:8:e8970. doi: 10.7717/peerj.8970. eCollection 2020.

Authors

Yu Xia^#¹, Xiao-Tao He^#¹, Xin-Yue Xu¹, Bei-Min Tian¹, Ying An¹, Fa-Ming Chen¹

Affiliation

¹ State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.

^# Contributed equally.

Abstract

Background: Different phenotypes of macrophages (M0, M1 and M2 Mφs) have been demonstrated to play distinct roles in regulating mesenchymal stem cells in various in vitro and in vivo systems. Our previous study also found that cell-conditioned medium (CM) derived from M1 Mφs supported the proliferation and adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), whereas CM derived from either M0 or M2 Mφs showed an enhanced effect on cell osteogenic differentiation. However, the underlying mechanism remains incompletely elucidated. Exosomes, as key components of Mφ-derived CM, have received increasing attention. Therefore, it is possible that exosomes may modulate the effect of Mφ-derived CM on the property of BMMSCs. This hypothesis was tested in the present study.

Methods: In this study, RAW264.7 cells were induced toward M1 or M2 polarization with different cytokines, and exosomes were isolated from the unpolarized (M0) and polarized (M1 and M2) Mφs. Mouse BMMSCs were then cultured with normal complete medium or inductive medium supplemented with M0-Exos, M1-Exos or M2-Exos. Finally, the proliferation ability and the osteogenic, adipogenic and chondrogenic differentiation capacity of the BMMSCs were measured and analyzed.

Results: We found that only the medium containing M1-Exos, rather than M0-Exos or M2-Exos, supported cell proliferation and osteogenic and adipogenic differentiation. This was inconsistent with CM-based incubation. In addition, all three types of exosomes had a suppressive effect on chondrogenic differentiation.

Conclusion: Although our data demonstrated that exosomes and CM derived from the same phenotype of Mφs didn't exert exactly the same cellular influences on the cocultured stem cells, it still confirmed the hypothesis that exosomes are key regulators during the modulation effect of Mφ-derived CM on BMMSC property.

Keywords: Bone marrow mesenchymal stem cells; Cell differentiation; Cell proliferation; Exosomes; Macrophages.

Grants and funding

This work was supported by the National Natural Science Foundation of China (Nos. 81700971, 81970947 and 81800971). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.