The Extracellular Matrix Enriched With Exosomes for the Treatment on Pulmonary Fibrosis in Mice

Yanzhen Yu; Xingzhi Liu; Zhe Zhao; Zhongjuan Xu; Yong Qiao; Yuanshuai Zhou; Hong Qiao; Junjie Zhong; Jianwu Dai; Guangli Suo

doi:10.3389/fphar.2021.747223

The Extracellular Matrix Enriched With Exosomes for the Treatment on Pulmonary Fibrosis in Mice

Front Pharmacol. 2021 Dec 6:12:747223. doi: 10.3389/fphar.2021.747223. eCollection 2021.

Authors

Yanzhen Yu^{1

2}, Xingzhi Liu^{1

2}, Zhe Zhao², Zhongjuan Xu^{1

2}, Yong Qiao², Yuanshuai Zhou³, Hong Qiao⁴, Junjie Zhong⁵, Jianwu Dai⁶, Guangli Suo²

Affiliations

¹ School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, China.
² CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
³ Jiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
⁴ Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX, United States.
⁵ Department of Neurosurgery, Fudan University Huashan Hospital, National Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ State Key Laboratory of Molecular, Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

Abstract

Pulmonary fibrosis (PF) is a severe respiratory disease caused by lung microenvironment changes. TGF-β/Smad3 signaling pathway plays a critical role in the fibrotic process. MicroRNA-29 (miR-29) has proved to alleviate the occurrence of PF by downregulating TGF-β/Smad3 signaling pathway. The miRNA application encounters obstacles due to its low stability in body and no targeting to lesions. Exosomes can be used for therapeutic delivery of miRNA due to their favorable delivery properties. However, low efficiency of separation and production impedes the therapeutic application of exosomes. In this study, we developed a liquid natural extracellular matrix (ECM) enriched with miR-29-loaded exosomes for PF treatment. The collagen-binding domain (CBD)-fused Lamp2b (CBD-Lamp2b) and miR-29 were overexpressed in human foreskin fibroblast (HFF) host cells for the entrapment of miR-29-loaded exosomes in ECM of the cells. The repeated freeze-thaw method was performed to prepare the liquid ECM enriched with exosomes without destroying the exosomal membrane. In summary, this study developed a novel functional ECM biomaterial for therapy of PF, and also provided a promising gene therapy platform for different diseases by treatment with liquid ECM that is, enriched with exosomes loaded with different functional miRNAs.

Keywords: collagen-binding domain; exosome; extracellular matrix; miR-29; pulmonary fibrosis.