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

Abstract

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.

Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)

“…The relevance of this research work spans beyond the development of novel therapeutic approaches to treat corneal injuries in horses, being also of great interest for the application in humans. In this regard, our results complement previous studies demonstrating the beneficial role of EVs in treating human corneal injuries [64,109,110], providing valuable insights for the advancement of this field.…”

Bone marrow mesenchymal stem cell‐derived extracellular vesicles promote corneal epithelial repair and suppress apoptosis via modulation of Caspase‐3 in vitro

“…The effect of BM-MSC-EVs on corneal epithelial repair was evaluated through in vitro wound healing assay [20,27,28]. HCECs were cultured in 12 well plates until 100% confluency.…”

AIM2 and Psoriasis

“…The trait of secretory, immunomodulatory, and homing properties of these cells contributes to the function of supporting immune cells, building immune memory and immunoregulatory properties as well as antimicrobial activity (126-128). Mesenchymal stromal cells can regulate innate and adaptive immune responses via inflammatory cytokines released into the microenvironment (129). Lin et al reported for the first time that when mesenchymal stromal cells were repeatedly exposed to lipopolysaccharide (LPS) in mice, the activation of NF-kB was increased significantly, enhancing the anti-inflammatory effect of macrophages, and this process was associated with histone methylation (130).…”

“…The trait of secretory, immunomodulatory, and homing properties of these cells contributes to the function of supporting immune cells, building immune memory and immunoregulatory properties as well as antimicrobial activity ( 126 – 128 ). Mesenchymal stromal cells can regulate innate and adaptive immune responses via inflammatory cytokines released into the microenvironment ( 129 ). Lin et al.…”