Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-ß signaling inhibition.
Stem Cell Res Ther
; 12(1): 230, 2021 04 12.
Article
in English
| MEDLINE | ID: covidwho-1192728
ABSTRACT
BACKGROUND:
Pulmonary fibrosis (PF), the end point of interstitial lung diseases, is characterized by myofibroblast over differentiation and excessive extracellular matrix accumulation, leading to progressive organ dysfunction and usually a terminal outcome. Studies have shown that umbilical cord-derived mesenchymal stromal cells (uMSCs) could alleviate PF; however, the underlying mechanism remains to be elucidated.METHODS:
The therapeutic effects of uMSC-derived extracellular vesicles (uMSC-EVs) on PF were evaluated using bleomycin (BLM)-induced mouse models. Then, the role and mechanism of uMSC-EVs in inhibiting myofibroblast differentiation were investigated in vivo and in vitro.RESULTS:
Treatment with uMSC-EVs alleviated the PF and enhanced the proliferation of alveolar epithelial cells in BLM-induced mice, thus improved the life quality, including the survival rate, body weight, fibrosis degree, and myofibroblast over differentiation of lung tissue. Moreover, these effects of uMSC-EVs on PF are likely achieved by inhibiting the transforming growth factor-ß (TGF-ß) signaling pathway, evidenced by decreased expression levels of TGF-ß2 and TGF-ßR2. Using mimics of uMSC-EV-specific miRNAs, we found that miR-21 and miR-23, which are highly enriched in uMSC-EVs, played a critical role in inhibiting TGF-ß2 and TGF-ßR2, respectively.CONCLUSION:
The effects of uMSCs on PF alleviation are likely achieved via EVs, which reveals a new role of uMSC-EV-derived miRNAs, opening a novel strategy for PF treatment in the clinical setting.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
Mesenchymal Stem Cells
/
Extracellular Vesicles
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Stem Cell Res Ther
Year:
2021
Document Type:
Article
Affiliation country:
S13287-021-02296-8
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