Bone marrow-versus adipose tissue-derived mesenchymal stem cells for corneal failure in an experimental model of limbal stem cell deficiency

Abstract

Ocular limbal stem cell deficiency (LSCD) occurs because of corneal epithelial stem cell destruction or dysfunction at the limbal niche. LSCD can cause corneal blindness, and the current therapy based on limbal stem cell transplantation is continuously improving. The aim of this work was to compare the safety and efficacy of human mesenchymal stem cells (hMSCs) derived from bone marrow (hBM-MSCs) and adipose tissue (hAT-MSCs) when transplanted to a rabbit model of LSCD. Both hMSC types expressed the corneal and limbal epithelial cell markers CK3, CK12, ZO-1, and ABCG2 under standard culture conditions. A few hBM-MSCs expressed CK7 and E- cadherin, while hAT-MSCs expressed more CK7 but no E-cadherin. The hMSCs were seeded onto amniotic membranes and transplanted onto the ocular surface of a LSCD rabbit model. Both hMSC types were well tolerated without immunosuppression and were primarily located in the superior limbal stroma eight weeks post- transplantation. The hBM-MSC–treated group showed less superficial neovascularization, while the hAT- MSC–treated group showed less conjunctival invasion and fewer corneal stromal blood vessels. Compared to the untreated LSCD group, both hMSC-treated groups had less corneal opacity, less corneal and limbal stromal inflammation, and more corneal epithelial layers that partially recovered the corneal and limbal epithelial markers CK3, CK15, and p63. Overall, transplantation of hBM-MSCs and hAT-MSCs in a rabbit LSCD model reduced the development of corneal opacity, neovascularization, inflammation, and partially restored corneal and limbal tissue structure and epithelial cell phenotypes. Therefore, both types of hMSCs could become valid alternatives for LSCD treatment.