Exosomes from 3D culture of marrow stem cells enhances endothelial cell proliferation, migration, and angiogenesis via activation of the HMGB1/AKT pathway

Wenling Gao; Tangzhao Liang; Ronghang He; Jianhua Ren; Hui Yao; Kun Wang; Lei Zhu; Yue Xu

doi:10.1016/j.scr.2020.102122

Exosomes from 3D culture of marrow stem cells enhances endothelial cell proliferation, migration, and angiogenesis via activation of the HMGB1/AKT pathway

Stem Cell Res. 2020 Dec 10:50:102122. doi: 10.1016/j.scr.2020.102122. Online ahead of print.

Authors

Wenling Gao¹, Tangzhao Liang², Ronghang He³, Jianhua Ren³, Hui Yao³, Kun Wang³, Lei Zhu⁴, Yue Xu⁵

Affiliations

¹ Department of Orthodontics, Hospital of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, 510060 Guangzhou, China. Electronic address: gaowling@mail.sysu.edu.cn.
² Department of Orthopaedic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, 510630 Guangzhou, China. Electronic address: liangtzh5@mail.sysu.edu.cn.
³ Department of Orthopaedic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, 510630 Guangzhou, China.
⁴ Department of Plastic and Reconstructive Surgery, the Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, 510630 Guangzhou, China. Electronic address: zhulei@mail.sysu.edu.cn.
⁵ Department of Orthodontics, Hospital of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, 510060 Guangzhou, China. Electronic address: xuyue@mail.sysu.edu.cn.

PMID: 33316600
DOI: 10.1016/j.scr.2020.102122

Abstract

Background: Angiogenesis is an essential step in tissue engineering. MSC exosomes play an important role in angiogenesis. Functional biomolecules in exosomes vested by the culture microenvironment can be transferred to recipient cells and affects their effect. 3D culture can improve the proliferation and activity of MSCs. However, whether exosomes derived from 3D culture of MSCs have an enhanced effect on angiogenesis is unclear.

Methods: Herein, we compared the bioactivity of exosomes produced by conventional 2D culture (2D-exos) and 3D culture (3D-exos) of bone marrow stem cells (BMSCs) in angiogenesis.

Results: A series of in vitro and in vivo experiments indicated that 3D-exos exhibited stronger effects on HUVEC cell proliferation, migration, tube formation, and in vivo angiogenesis compared with 2D-exos. Moreover, the superiority of 3D-exos might be attributed to the activation of HMGB1/AKT signaling.

Conclusions: These results indicate that exosomes from 3D culture of MSCs may serve as a potential therapeutic approach for pro-angiogenesis.

Keywords: 3D culture; Angiogenesis; Bone marrow stem cell; Exosome; HUVEC.