Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-β signaling inhibition.
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-β (TGF-β) signaling pathway, evidenced by decreased expression levels of TGF-β2 and TGF-βR2. 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-β2 and TGF-βR2, 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.
['Shi|Liyan|L|', 'Ren|Jing|J|', 'Li|Jiping|J|', 'Wang|Dongxu|D|', 'Wang|Yusu|Y|', 'Qin|Tao|T|', 'Li|Xiuying|X|', 'Zhang|Guokun|G|', 'Li|Chunyi|C|', 'Wang|Yimin|Y|0000-0002-5110-0859']
D000818:Animals D001761:Bleomycin D000067128:Extracellular Vesicles D059630:Mesenchymal Stem Cells D051379:Mice D011658:Pulmonary Fibrosis D015398:Signal Transduction D016212:Transforming Growth Factor beta D015291:Transforming Growth Factors D014470:Umbilical Cord
Extracellular vesicles Pulmonary fibrosis Transforming growth factor-β Umbilical cord-derived mesenchymal stromal cells