Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

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 Decapent...

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Autores principales:	Zhenyuan Wei, Yang Zhao, Peichun Hsu, Shang Guo, Chi Zhang, Biao Zhong
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Gene therapy SMAD7 exosome endothelial-mesenchymal transition mouse aortic endothelial cells endothelial cell targeting property Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/ff8018cd0a0b4418be8ec211d33944c9
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spelling	oai:doaj.org-article:ff8018cd0a0b4418be8ec211d33944c92021-12-05T12:18:18ZExosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells10.1186/s12891-021-04896-01471-2474https://doaj.org/article/ff8018cd0a0b4418be8ec211d33944c92021-11-01T00:00:00Zhttps://doi.org/10.1186/s12891-021-04896-0https://doaj.org/toc/1471-2474Abstract 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-AbCD34 could be stably stored at 4°C and 37°C for at least 8 days. Exosome-DSPE-PEG-AbCD34 has better targeting property to MAEC cells and can enter into the cells more effectively. The Exosome-DSPE-PEG-AbCD34 -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.Zhenyuan WeiYang ZhaoPeichun HsuShang GuoChi ZhangBiao ZhongBMCarticleGene therapySMAD7exosomeendothelial-mesenchymal transitionmouse aortic endothelial cellsendothelial cell targeting propertyDiseases of the musculoskeletal systemRC925-935ENBMC Musculoskeletal Disorders, Vol 22, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gene therapy SMAD7 exosome endothelial-mesenchymal transition mouse aortic endothelial cells endothelial cell targeting property Diseases of the musculoskeletal system RC925-935
spellingShingle	Gene therapy SMAD7 exosome endothelial-mesenchymal transition mouse aortic endothelial cells endothelial cell targeting property Diseases of the musculoskeletal system RC925-935 Zhenyuan Wei Yang Zhao Peichun Hsu Shang Guo Chi Zhang Biao Zhong Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
description	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-AbCD34 could be stably stored at 4°C and 37°C for at least 8 days. Exosome-DSPE-PEG-AbCD34 has better targeting property to MAEC cells and can enter into the cells more effectively. The Exosome-DSPE-PEG-AbCD34 -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.
format	article
author	Zhenyuan Wei Yang Zhao Peichun Hsu Shang Guo Chi Zhang Biao Zhong
author_facet	Zhenyuan Wei Yang Zhao Peichun Hsu Shang Guo Chi Zhang Biao Zhong
author_sort	Zhenyuan Wei
title	Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
title_short	Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
title_full	Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
title_fullStr	Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
title_full_unstemmed	Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
title_sort	exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ff8018cd0a0b4418be8ec211d33944c9
work_keys_str_mv	AT zhenyuanwei exosomesforgenetherapyeffectivelyinhibittheendothelialmesenchymaltransitioninmouseaorticendothelialcells AT yangzhao exosomesforgenetherapyeffectivelyinhibittheendothelialmesenchymaltransitioninmouseaorticendothelialcells AT peichunhsu exosomesforgenetherapyeffectivelyinhibittheendothelialmesenchymaltransitioninmouseaorticendothelialcells AT shangguo exosomesforgenetherapyeffectivelyinhibittheendothelialmesenchymaltransitioninmouseaorticendothelialcells AT chizhang exosomesforgenetherapyeffectivelyinhibittheendothelialmesenchymaltransitioninmouseaorticendothelialcells AT biaozhong exosomesforgenetherapyeffectivelyinhibittheendothelialmesenchymaltransitioninmouseaorticendothelialcells
_version_	1718372112869097472

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

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