Improving the immunomodulatory function of mesenchymal stem cells by defined chemical approach

Jintao Cheng; Yuan Feng; Xiao Feng; Donghao Wu; Xu Lu; Zhihua Rao; Cuiping Li; Nan Lin; Changchang Jia; Qi Zhang

doi:10.3389/fimmu.2022.1005426

Improving the immunomodulatory function of mesenchymal stem cells by defined chemical approach

Front Immunol. 2022 Sep 20:13:1005426. doi: 10.3389/fimmu.2022.1005426. eCollection 2022.

Authors

Jintao Cheng¹, Yuan Feng², Xiao Feng³, Donghao Wu⁴, Xu Lu³, Zhihua Rao⁵, Cuiping Li¹, Nan Lin², Changchang Jia¹, Qi Zhang¹

Affiliations

¹ Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Tangxia Laboratory, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Mesenchymal stem cell (MSC) is a potential therapeutic material that has self-renewal, multilineage differentiation, and immunomodulation properties. However, the biological function of MSCs may decline due to the influence of donor differences and the in vitro expansion environment, which hinders the advancement of MSC-based clinical therapy. Here, we investigated a method for improving the immunomodulatory function of MSCs with the help of small-molecule compounds, A-83-01, CHIR99021, and Y27632 (ACY). The results showed that small-molecule induced MSCs (SM-MSCs) could enhance their immunosuppressive effects on T cells and macrophages. In vivo studies showed that, in contrast to control MSCs (Ctrl-MSCs), SM-MSCs could inhibit the inflammatory response in mouse models of delayed hypersensitivity and acute peritonitis more effectively. In addition, SM-MSCs showed the stronger ability to inhibit the infiltration of pro-inflammatory T cells and macrophages. Thus, small-molecule compounds ACY could better promote the immunomodulatory effect of MSCs, indicating it could be a potential improving method in MSC culture.

Keywords: cell therapy; immunomodulation; inflammatory cytokines; mesenchymal stem cells; small-molecule compounds.

Publication types

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

MeSH terms

Animals
Cell Differentiation
Immunomodulation* / physiology
Macrophages
Mesenchymal Stem Cells*
Mice
T-Lymphocytes