Exosomes-loaded thermosensitive hydrogels for corneal epithelium and stroma regeneration

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 ste...

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Bibliographic Details
Published in:Biomaterials 2022-01, Vol.280, p.121320-121320, Article 121320
Main Authors: Tang, Qiaomei, Lu, Bing, He, Jian, Chen, Xiao, Fu, Qiuli, Han, Haijie, Luo, Chenqi, Yin, Houfa, Qin, Zhenwei, Lyu, Danni, Zhang, Lifang, Zhou, Min, Yao, Ke
Format: Article
Language:English
Subjects:
Cicatrix - metabolism
Cornea regeneration
Corneal Stroma
Drug release
Epithelium, Corneal
Exosome
Exosomes - metabolism
Humans
Hydrogels - pharmacology
Membrane Glycoproteins - metabolism
Mesenchymal Stem Cells - metabolism
microRNA
Regeneration
Thermosensitive hydrogels
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Summary: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 extracellular 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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2021.121320