Exosomes for Gene Therapy Effectively Inhibit the Endothelial-mesenchymal Transition in Mouse Aortic Endothelial Cells

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2021 Dec 1

PMID 34847881

Citations 5

Authors

Zhenyuan Wei

Yang Zhao

Peichun Hsu

Shang Guo

Chi Zhang

Biao Zhong

Affiliations

Soon will be listed here.

Abstract

Background: Heterotopic ossification (HO) can limit joint activity, causes ankylosis and impairs the function and rehabilitation of patients. Endothelial to mesenchymal transition (EndMT) plays an important role in the pathogenesis of HO, and high expression of SMAD7(Mothers Against Decapentaplegic Homolog 7) in endothelial cells can effectively reverse the TGF-β1 mediated EndMT. This article studied an appropriately engineered exosome with high biocompatibility and good targeting property to administrate SMAD7 gene therapy to inhibit the EndMT.

Methods: Exosomes from mouse aortic endothelial cells were cultured and harvested. DSPE-PEG and antibody CD34 were combined to exosomes to synthesize the endothelial cell targeting exosome vector (Exosome-DSPE-PEG-AbCD34). The biocompatibility, stability, targeting and cell internalization of exosome vector were tested, then the Exosome-DSPE-PEG-AbCD34 was loaded with Smad7 plasmid and administrated to MAECs to examine its therapeutic effect on EndMT of MAEC mediated by TGF-β1.

Results: The Exosome-DSPE-PEG-AbCD34 has no impact on MAEC cell viability at high concentration, and exosome-DSPE-PEG-Ab could be stably stored at 4°C and 37°C for at least 8 days. Exosome-DSPE-PEG-Ab has better targeting property to MAEC cells and can enter into the cells more effectively. The Exosome-DSPE-PEG-Ab-Smad7 could significantly increase the level of SMAD7, decrease the expression of TGF-β1, and effectively reverse the EndMT of MAEC mediated by TGF- β1 in MAEC cells.

Conclusions: The synthesized Exosome-DSPE-PEG-AbCD34-Smad7 has good biological properties and can effectively reverse the EndMT of MAEC mediated by TGF-β1. Thus, Exosome-DSPE-PEG-AbCD34-Smad7 may has the potential for the prevention and treatment of HO.

Citing Articles

Heterotopic ossification: Current developments and emerging potential therapies.

Bei M, Cao Q, Zhao C, Xiao Y, Chen Y, Xiao H Chin Med J (Engl). 2025; 138(4):389-404.

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Advances in regulating endothelial-mesenchymal transformation through exosomes.

Sishuai S, Lingui G, Pengtao L, Xinjie B, Junji W Stem Cell Res Ther. 2024; 15(1):391.

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Engineered bone marrow mesenchymal stem cell-derived exosomes loaded with miR302 through the cardiomyocyte specific peptide can reduce myocardial ischemia and reperfusion (I/R) injury.

Gu J, You J, Liang H, Zhan J, Gu X, Zhu Y J Transl Med. 2024; 22(1):168.

PMID: 38368334 PMC: 10874538. DOI: 10.1186/s12967-024-04981-7.

Nintedanib-loaded exosomes from adipose-derived stem cells inhibit pulmonary fibrosis induced by bleomycin.

Cai L, Wang J, Yi X, Yu S, Wang C, Zhang L Pediatr Res. 2024; 95(6):1543-1552.

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Recent developments in isolating methods for exosomes.

Gao J, Li A, Hu J, Feng L, Liu L, Shen Z Front Bioeng Biotechnol. 2023; 10:1100892.

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