Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-β signaling inhibition.

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-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.

• Authors: Liyan Shi, Jing Ren, Jiping Li, Dongxu Wang, Yusu Wang, Tao Qin, Xiuying Li, Guokun Zhang, Chunyi Li, Yimin Wang
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 12 Issue 1 Pg. 230 (04 12 2021) ISSN: 1757-6512 [Electronic] England
• PMID: 33845892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transforming Growth Factor beta
• Bleomycin
• Transforming Growth Factors

Topics

• Animals
• Bleomycin (toxicity)
• Extracellular Vesicles
• Mesenchymal Stem Cells
• Mice
• Pulmonary Fibrosis (chemically induced, genetics, therapy)
• Signal Transduction
• Transforming Growth Factor beta (genetics)
• Transforming Growth Factors
• Umbilical Cord