Journal
BIOMATERIALS
Volume 280, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121320
Keywords
Exosome; Thermosensitive hydrogels; Drug release; Cornea regeneration; microRNA
Funding
- Zhejiang Provincial Natural Science Foundation of China [LQ20H120009]
- Organ Reconstruction and Manufacturing, Stra-tegic Priority Research Program of the Chinese Academy of Sciences [XDA16010304]
- National Natural Science Foundation [81870641, 82070939, 81971667]
- Key Research and Development Project of Zhejiang Province [2020C03035]
- Core Facility, Zhejiang University School of Medicine
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In this study, a novel approach based on exosomes and a thermosensitive hydrogel was developed for the treatment of corneal diseases. This method effectively reduces scar formation and accelerates the healing process by promoting the repair of damaged corneal epithelium and stromal layer.
Corneal damage forms scar tissue and manifests as permanent corneal opacity, which is the main cause of visual impairment caused by corneal diseases. To treat these diseases, herein, we developed a novel approach based on the exosome derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) combined with a thermosensitive hydrogel, which reduces scar formation and accelerates the healing process. We found that a thermosensitive chitosan-based hydrogels (CHI hydrogel) sustained-release iPSC-MSC exosomes can effectively promote the repair of damaged corneal epithelium and stromal layer, downregulating mRNA expression coding for the three most enriched collagens (collagen type I alpha 1, collagen type V alpha 1 and collagen type V alpha 2) in corneal stroma and reducing scar formation in vivo. Furthermore, iPSC-MSCs secrete exosomes that contain miR-432-5p, which suppresses translocation-associated membrane protein 2 (TRAM2), a vital modulator of the collagen biosynthesis in the corneal stromal stem cells to avert the deposition of extra cellular matrix (ECM). Our findings indicate that iPSC-MSCs secrete miRNA-containing exosomes to promote corneal epithelium and stroma regeneration, and that miR-432-5p can prevent ECM deposition via a mechanism most probably linked to direct repression of its target gene TRAM2. Overall, our exosomes-based thermosensitive CHI hydrogel, is a promising technology for clinical therapy of various corneal diseases.
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