Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes

Journal of Nanobiotechnology

Xiaohua Xu¹  Huiying Lv²  Jing Li²  Liya Wu²  Jinlan Jiang²  Xiuying Li²  Ying Wang²  Zhenhong Wei²  Liyan Shi²  Hao Zhang³  Bai Yang³  Binxi Li³ 

[1] Department of Nephrology, China-Japan Union Hospital of Jilin University;Scientific Research Center, China-Japan Union Hospital of Jilin University;State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University;

关键词: Exosome;    Iron oxide nanoparticle;    Mesenchymal stem cell;    Cutaneous wound;   

DOI  :  10.1186/s12951-020-00670-x

来源: DOAJ

【 摘 要 】

Abstract Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

【 授权许可】

Unknown