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
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.