The Extracellular Matrix Enriched With Exosomes for the Treatment on Pulmonary Fibrosis in Mice
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Published on: April 30, 2019
Yanzhen Yu1,2, Xingzhi Liu1,2, Zhe Zhao2
1School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 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.
Insights
This study presents a novel liquid extracellular matrix (ECM) biomaterial for pulmonary fibrosis (PF) treatment. It effectively delivers microRNA-29 (miR-29) via exosomes, offering a promising gene therapy platform.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Respiratory Medicine
Background:
- Pulmonary fibrosis (PF) is a severe lung disease driven by microenvironment changes.
- The TGF-β/Smad3 pathway is crucial in fibrosis, and miR-29 can inhibit it.
- Current miRNA delivery faces challenges with stability and targeting, while exosome production is inefficient.
Purpose of the Study:
- To develop a novel therapeutic strategy for pulmonary fibrosis using a functional biomaterial.
- To create a delivery system for microRNA-29 (miR-29) that overcomes current limitations.
- To establish a versatile platform for exosome-based gene therapy.
Main Methods:
- Engineered human foreskin fibroblast (HFF) cells to overexpress miR-29 and a collagen-binding domain (CBD)-fused Lamp2b.
- Loaded miR-29 into exosomes produced within the HFF cells.
- Prepared a liquid extracellular matrix (ECM) enriched with these miR-29-loaded exosomes using a freeze-thaw method.
Main Results:
- Successfully developed a liquid ECM biomaterial incorporating miR-29-loaded exosomes.
- The preparation method preserved exosomal integrity.
- Demonstrated a novel approach for exosome-based therapeutic delivery.
Conclusions:
- A novel functional ECM biomaterial was created for pulmonary fibrosis therapy.
- This approach offers a promising platform for exosome-mediated gene therapy for various diseases.
- The developed biomaterial enhances miRNA delivery for potential therapeutic applications.
