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Extracellular vesicles derived from EphB2-overexpressing bone marrow mesenchymal stem cells ameliorate DSS-induced colitis by modulating immune balance

Authors :
Ting Yu
Si Chu
Xingxing Liu
Junyi Li
Qianyun Chen
Meng Xu
Hui Wu
Mingyue Li
Yalan Dong
Feng Zhu
Haifeng Zhou
Desheng Hu
Heng Fan
Source :
Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-14 (2021)
Publication Year :
2021
Publisher :
BMC, 2021.

Abstract

Abstract Background The bone marrow mesenchymal stem cell (BMSCs)-derived extracellular vesicles (EVs) open up a new avenue for ulcerative colitis (UC) treatment recently, but they are not selectively enriched in targeted tissues. EphB2, a cell-to-cell signaling receptor, is identified as a regulator for inflammatory response, immune homeostasis and cell migration. In this study, we investigated the therapeutic potential and underlying mechanism for EphB2 over-expressing BMSCs derived EVs (EphB2-EVs) in the treatment of UC. Methods BMSCs and EVs were obtained and characterized by a series of experiments. Lentivirus vector encoding EphB2 was transfected into BMSCs and verified by qRT-PCR. We analyzed the EphB2-EVs ability of colonic targeting in a DSS-induced colitis model by using confocal microscope and WB. The protective effect of EphB2-EVs in vivo was systematically evaluated by using a series of function experiments. Results We successfully constructed EphB2-overexpressing BMSCs derived EVs (EphB2-EVs). Overexpression of EphB2 significantly enhanced the homing of EVs to the damaged colon. In addition, EphB2-EVs were effective to attenuate inflammation in intestinal mucosa and restore the damaged colon tissue by inhibiting the release of proinflammatory cytokines and upregulating the anti-inflammatory mediators. EphB2-EVs effectively reduced the oxidative stress and repaired the intestinal mucosal barrier in the UC rats. Moreover, EphB2-EVs demonstrated a robust immunomodulatory effect to restore immune homeostasis via modulating Th17/Treg balance and restraining STAT3 activation. Conclusions Our results suggest that EphB2-EVs have high colonic targeting ability and could mitigate DSS-induced colitis via maintaining colonic immune homeostasis. These findings provide an effective therapeutic strategy for UC treatment in clinic.

Details

Language :
English
ISSN :
17576512
Volume :
12
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Stem Cell Research & Therapy
Publication Type :
Academic Journal
Accession number :
edsdoj.7c783d897f54538a3e98b027f563a72
Document Type :
article
Full Text :
https://doi.org/10.1186/s13287-021-02232-w