Role of Mesenchymal Stem Cells on Cornea Wound Healing Induced by Acute Alkali Burn

Abstract

The aim of this study was to investigate the effects of subconjunctivally administered mesenchymal stem cells (MSCs) on corneal wound healing in the acute stage of an alkali burn. A corneal alkali burn model was generated by placing a piece of 3-mm diameter filter paper soaked in NaOH on the right eye of 48 Sprague-Dawley female rats. 24 rats were administered a subconjunctival injection of a suspension of 2×106 MSCs in 0.1 ml phosphate-buffered saline (PBS) on day 0 and day 3 after the corneal alkali burn. The other 24 rats were administered a subconjunctival injection of an equal amount of PBS as a control. Deficiencies of the corneal epithelium and the area of corneal neovascularization (CNV) were evaluated on days 3 and 7 after the corneal alkali burn. Infiltrated CD68+ cells were detected by immunofluorescence staining. The mRNA expression levels of macrophage inflammatory protein-1 alpha (MIP-1α), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) were analyzed using real-time polymerase chain reaction (real-time PCR). In addition, VEGF protein levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). MSCs significantly enhanced the recovery of the corneal epithelium and decreased the CNV area compared with the control group. On day 7, the quantity of infiltrated CD68+ cells was significantly lower in the MSC group and the mRNA levels of MIP-1α, TNF-α, and VEGF and the protein levels of VEGF were also down-regulated. However, the expression of MCP-1 was not different between the two groups. Our results suggest that subconjunctival injection of MSCs significantly accelerates corneal wound healing, attenuates inflammation and reduces CNV in alkaline-burned corneas; these effects were found to be related to a reduction of infiltrated CD68+ cells and the down-regulation of MIP-1α, TNF-α and VEGF.

Modulation of the Early Inflammatory Microenvironment in the Alkali-Burned Eye by Systemically Administered Interferon-γ-Treated Mesenchymal Stromal Cells

“…Further, we found that MSCs pretreated with IFN-g suppressed the infiltration of the damaged eye by CD14 + , CD80 + , and CD11b + Gr-1 + myeloid populations even more effectively than they inhibited infiltration by lymphoid cells. These results are in agreement with the findings of Yao et al [18], who showed that the number of CD68 + cells infiltrating the site of injury on day 7 was significantly lower in a group treated with MSCs [18]. In addition, the systemic injection of human MSCs significantly reduced the infiltration of neutrophils into the cornea on days 1 and 3 after injury in a rat model of a chemically burned eye [19].…”

“…It has been shown that the curative effect of MSCs on corneal injury can consist partly in the epithelial transdifferentiation of MSCs [7,15] and in the suppression of corneal inflammation [16][17][18][19].…”

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

“…A recent report has shown that systemically administered human MSCs reduced corneal inflammatory damage without engraftment by secreting anti-inflammatory factors in response to injury signals from the cornea [43] . Alternatively, MSCs may be administered locally to improve the concentration at the injured cornea through subconjunctival administration of MSCs [44] and through transplantation of MSCs with the amniotic membrane (AM) [45,46] and a hollow plastic tube onto the cornea [47] . Differentiation into corneal tissue LSC transplantation, the currently available treatment for severe corneal epithelium damage, has certain limitations.…”

Dynamics of Morphological Changes in the Anterior Segment of the Rat Eye after Experimental Alkali Burn Depending on the Acetylator Phenotype

“…However, the structural and functional restoration of alkali burn-injuries to the cornea remains a challenge, despite these therapies and thus prompting the search for novel treatment strategies [7][8][9]. A detailed study of regenerative processes under the influence of various drugs is a top priority of modern ophthalmology.…”