Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Promote Corneal Wound Repair by Regulating Inflammation and Angiogenesis

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 23; p. 3892
• Main Authors: Saccu, Gabriele, Menchise, Valeria, Gai, Chiara, Bertolin, Marina, Ferrari, Stefano, Giordano, Cristina, Manco, Marta, Dastrù, Walter, Tolosano, Emanuela, Bussolati, Benedetta, Calautti, Enzo, Camussi, Giovanni, Altruda, Fiorella, Fagoonee, Sharmila
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-12-2022; MDPI
• Subjects: Analysis; Angiogenesis; Animal models; Animals; Antibodies; Blood & organ donations; Bone Marrow; Cadavers; Care and treatment; Cell culture; Cell death; Cornea; Corneal Injuries - metabolism; Corneal Injuries - therapy; Corneal transplantation; Disease; Epithelial cells; Extracellular vesicles; Extracellular Vesicles - metabolism; Flow cytometry; Gd-AAZTA-MADEC; Health aspects; Humans; Inflammation; Inflammation - metabolism; Magnetic resonance imaging; Mesenchymal Stem Cells - metabolism; mesenchymal stromal/stem cells; Mesenchyme; Methods; Methylcellulose; Mice; Microscopy; MRI; Patient compliance; Quality of life; Stem cells; Wound healing; Wounds and injuries; Italy; St Louis Missouri; Basel Switzerland; United States > US; Switzerland; Germany; Indianapolis Indiana; methylcellulose; extracellular vesicles; MRI; cornea; Esrp1; Gd-AAZTA-MADEC; mesenchymal stromal/stem cells
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11233892

Severe corneal damage leads to complete vision loss, thereby affecting life quality and impinging heavily on the healthcare system. Current clinical approaches to manage corneal wounds suffer from severe drawbacks, thus requiring the development of alternative strategies. Of late, mesenchymal stromal/stem cell (MSC)-derived extracellular vesicles (EVs) have become a promising tool in the ophthalmic field. In the present study, we topically delivered bone-marrow-derived MSC-EVs (BMSC-EVs), embedded in methylcellulose, in a murine model of alkali-burn-induced corneal damage in order to evaluate their role in corneal repair through histological and molecular analyses, with the support of magnetic resonance imaging. Our data show that BMSC-EVs, used for the first time in this specific formulation on the damaged cornea, modulate cell death, inflammation and angiogenetic programs in the injured tissue, thus leading to a faster recovery of corneal damage. These results were confirmed on cadaveric donor-derived human corneal epithelial cells in vitro. Thus, BMSC-EVs modulate corneal repair dynamics and are promising as a new cell-free approach for intervening on burn wounds, especially in the avascularized region of the eye.