Concise Reviews: Can Mesenchymal Stromal Cells Differentiate into Corneal Cells? A Systematic Review of Published Data

Abstract

The majority of stem cell therapies for corneal repair are based upon the use of progenitor cells isolated from corneal tissue, but a growing body of literature suggests a role for mesenchymal stromal cells (MSC) isolated from noncorneal tissues. While the mechanism of MSC action seems likely to involve their immuno-modulatory properties, claims have emerged of MSC transdifferentiation into corneal cells. Substantial differences in methodology and experimental outcomes, however, have prompted us to perform a systematic review of the published data. Key questions used in our analysis included: the choice of markers used to assess corneal cell phenotype, the techniques used to detect these markers, adequate reporting of controls, and tracking of MSC when studied in vivo. Our search of the literature revealed 28 papers published since 2006, with half appearing since 2012. MSC cultures established from bone marrow and adipose tissue have been best studied (22 papers). Critically, only 11 studies used appropriate markers of corneal cell phenotype, along with necessary controls. Ten out of these eleven papers, however, contained positive evidence of corneal cell marker expression by MSC. The clearest evidence is observed with respect to expression of markers for corneal stromal cells by MSC. In comparison, the evidence for MSC conversion into either corneal epithelial cells or corneal endothelial cells is often inconsistent or inconclusive. Our analysis clarifies this emerging body of literature and provides guidance for future studies of MSC differentiation within the cornea as well as other tissues. STEM CELLS 2015;33:785-791

The potential therapeutic effect of stem cells loaded on two different vehicles (amniotic membrane and platelet rich plasma gel) in experimentally induced corneal alkali burns in rats

“…These findings are in agreement with Harkin et al, (2015) who reported that BM-MSCs enhanced epithelial healing. This occured through various ways by which the MSCs reconstructed the corneal injuries after corneal alkali burn by growth factors and cytokines secretions which regulated cell proliferation and signaling.…”

Wound Repair and Regeneration

“…MSCs derived from bone marrow, adipose tissue, umbilical cord or dental pulp [211,212] were demonstrated to acquire both epithelial cell-like [213,214] and keratocyte-like characteristics [215][216][217] (see [195] for a systematic review). The therapeutic use of bone-marrow or adipose tissue-derived MSCs, by local injection or topical application in animal models of chemical burns, was shown to improve corneal healing and reduce corneal inflammation and neovascularization [218][219][220][221].…”

Limbal epithelial stem cells in regeneration of corneal epithelium – clinical and molecular aspects

“…Innym białkiem obecnym w LESC jest cytokeratyna 19 (CK19). Również w tym wypadku nie występuje ona wyłącznie w rogówce, dlatego podobnie jak p63 nie może być markerem specyficznym narządowo [13,23,26]. Markerem zwią-zanym z komórkami progenitorowymi nabłonka rogówki jest białko transporterowe z nadrodziny ABC typu G2 (ABCG2), uniwersalny marker komórek macierzystych [27,28].…”

“…Białka α9-, α6-, β1-integryny [23], cytokeratyna 15 (CK15), cytokeratyna 14 (CK14) [13] oraz receptor EGFR również używane są jako markery komórek progenitorowych rąbka rogów-ki [16]. Potwierdzono natomiast, że komórki warstwy epitelialnej rogówki wykazują ekspresję cytokeratyny 3 (CK3) oraz cytokeratyny 12 (CK12) [26,27,28,29]. Nie stwierdzono obecności tych białek w komórkach epitelialnych pochodzących z rąbka rogówki [23,30,31].…”