MSCs helped reduce scarring in the cornea after fungal infection when combined with anti-fungal treatment

Abstract

BackgroundFungal Keratitis (FK) is an infective keratopathy with extremely high blindness rate. The damaging effect of this disease is not only the destruction of corneal tissue during fungal infection, but also the cornea scar formed during the healing period after infection control, which can also seriously affect a patient’s vision. The purpose of the study was to observe the effect of umbilical cord mesenchymal stem cells (uMSCs) on corneal scar formation in FK.MethodsThe FK mouse model was made according to a previously reported method. Natamycin eye drops were used for antifungal treatment 24 h after modeling. There are four groups involved in the study, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. Mice in uMSCsinj FK group received repeated subconjunctival injections of uMSCs for 3 times at the 1d, 4d and 7d after FK modeling. At 14d, 21d and 28d after trauma, clinical observation, histological examination, second harmonic generation and molecular assays were performed.ResultsThe uMSCs topical administration reduced corneal scar formation area and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFβ1, CTGF, and COLI and finally inhibited phosphorylation of TGFβ1/Smad2 signaling pathway during FK corneal fibrosis.ConclusionThe results confirmed that uMSCs can improve corneal opacity during the scar formation stage of FK, and exert anti-inflammatory and anti-fibrotic effects.

Experimental Models for Fungal Keratitis: An Overview of Principles and Protocols

“…In addition to drugs or compounds, cells can also be delivered to the cornea via sub-conjunctival injection. For example, Zhou and colleagues found that corneal scar resolution following Fusarium keratitis was improved by the administration of topical natamycin in combination with subconjunctival injections of umbilical cord mesenchymal stem cells [57]. In this study, infection was induced by scratching the cornea with a needle and toothpick and then applying F. oxysporum hyphae to the surface [57].…”

“…Second harmonic generation microscopy allowed Zhou et al to assess the integrity of the cornea during infection. In this technique, a strong signal indicates a healthy arrangement of collagen fibers, while a weak signal indicated a disordered collagen disruption [57]. Abou Shousha et al used optical coherence tomography (OCT) to quantify corneal thickness (edema) during FK in rats [65].…”

“…Inflammation: Inflammation is a key driver of FK pathology and can be assessed through a variety of techniques. Flow cytometry provides the most direct readout by enumerating various fluorescently immunolabeled cell populations within whole corneas at defined time points [52,57,58]. Various proteins or peptides released by activated leukocytes may serve as a readout for the extent of inflammation.…”

Therapeutic Potential of Extracellular Vesicles for the Treatment of Corneal Injuries and Scars

“… 50 MSCs derived from amniotic membrane and adipose tissues also have antifibrotic effects in animal models of chemical injuries and fungal infection, respectively. 51 , 52 Subsequently, the Funderburgh research group at the University of Pittsburgh isolated and characterized corneal stromal/mesenchymal stem cells (CSSCs), which are MSCs within the human limbus. 53 CSSCs have the potency of multilineage differentiation and have the highest differentiation potential to keratocytes than do MSCs derived from adipose tissue, umbilical cord, or bone marrow.…”

Current stem cells technologies used in medicine

“…Umbilical cord mesenchymal stem cells (uMSCs) derived from the Wharton's Jelly, injected subconjunctivally, reduced corneal scar formation in the treatment of fungal keratitis (FK) in a mouse model. Injection of uMSCs was combined with antifungal treatment [85].…”