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Nintedanib-loaded exosomes from adipose-derived stem cells inhibit pulmonary fibrosis induced by bleomycin

Pediatric Research (2024)Cite this article

Abstract

Background

Pulmonary fibrosis (PF) is a progressive lung disorder with a high mortality rate; its therapy remains limited due to the inefficiency of drug delivery. In this study, the system of drug delivery of nintedanib (Nin) by exosomes derived from adipose-derived stem cells (ADSCs-Exo, Exo) was developed to effectively deliver Nin to lung lesion tissue to ensure enhanced anti-fibrosis therapy.

Methods

The bleomycin (BLM)-induced PF model was constructed in vivo and in vitro. The effects of Exo-Nin on BLM-induced PF and its regulatory mechanism were examined using RT-qPCR, Western blotting, immunofluorescence, and H&E staining.

Results

We found Exo-Nin significantly improved BLM-induced PF in vivo and in vitro compared to Nin and Exo groups alone. Mechanistically, Exo-Nin alleviated fibrogenesis by suppressing endothelial–mesenchymal transition through the down-regulation of the TGF-β/Smad pathway and the attenuation of oxidative stress in vivo and in vitro.

Conclusions

Utilizing adipose stem cell-derived exosomes as carriers for Nin exhibited a notable enhancement in therapeutic efficacy. This improvement can be attributed to the regenerative properties of exosomes, indicating promising prospects for adipose-derived exosomes in cell-free therapies for PF.

Impact

  • The system of drug delivery of nintedanib (Nin) by exosomes derived from adipose-derived stem cells was developed to effectively deliver Nin to lung lesion tissue to ensure enhanced anti-fibrosis therapy.

  • The use of adipose stem cell-derived exosomes as the carrier of Nin may increase the therapeutic effect of Nin, which can be due to the regenerative properties of the exosomes and indicate promising prospects for adipose-derived exosomes in cell-free therapies for PF.

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Fig. 1: Identification and Characterization of ADSCs and Exo-Nin.
Fig. 2: Role of Exo-Nin in BLM-induced PF in mice.
Fig. 3: Exo-Nin treatment alleviates BLM-induced EndoMT.
Fig. 4: Exo-Nin regulates BLM-induced EndoMT via TGF-β1/Smad pathway axis.
Fig. 5: Exo-Nin reduces oxidative stress induced by BLM.
Fig. 6: Scheme of Nin-loaded Exo preparation and PF therapy.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors gratefully acknowledge the financial supports by the Educational Commission of Fujian Province (No. JAT200702), as well as the Xiamen Medical College (No. K2020-05).

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Authors and Affiliations

  1. Department of Basic Medicine, Institute of Respiratory Diseases, Xiamen Medical College, Xiamen, China

    Liyun Cai, Jie Wang, Xue Yi, Shuwei Yu, Chong Wang, Liyuan Zhang, Xiaoling Zhang, Lixian Cheng, Wenwen Ruan, Feige Dong, Ping Su & Ying Shi

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Cai, L., Wang, J., Yi, X. et al. Nintedanib-loaded exosomes from adipose-derived stem cells inhibit pulmonary fibrosis induced by bleomycin. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03024-7

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