Efficacy of bone marrow- versus adipose tissue-derived mesenchymal stem cells in a rabbit model of limbal stem cell deficiency

Abstract

Purpose : Our research group has recently demonstrated that transplantation of bone marrow-derived mesenchymal stem cells (BM-MSC) onto the ocular surface of patients suffering from limbal stem cell deficiency (LSCD) can safely and effectively help repair the corneal epithelium (ClinicalTrials.gov: NCT01562002). However, adipose tissue-derived MSC (AT-MSC) are more accessible, more cost-effective and a safer source of MSC than bone marrow. The aim of this work was to compare the efficacy of BM-MSC versus AT-MSC for the treatment of ocular surface failure due to LSCD in rabbits.

Methods : A model of LSCD was induced in 27 New Zealand white rabbits by N-heptanol-based corneal denudation followed by a 360^○ surgical limbal peritomy. After 3 weeks, 250,000 MSC seeded on amniotic membrane were transplanted onto the ocular surface of 18 rabbits (9 with BM-MSC; 9 with AT-MSC). Nine non-transplanted animals formed the control group. Conjunctival invasion, corneal neovascularization, opacification, and epithelial defects were examined on a weekly basis on a slit lamp. Histopathology analyses at the end of follow-up (11 weeks) evaluated the level of tissue damage and the presence of lymphocytes (as a sign of inflammation) and goblet cells (as a sign of conjunctival in-growth) in limbal and corneal areas.

Results : The BM-MSC-transplanted group showed less neovascularization and less corneal opacity at weeks 6-8, and 6-9, respectively than the untreated group. The AT-MSC-treated group had less conjunctival invasion and corneal opacity at weeks 6-8 and 6-10, respectively than the control group. There were no differences in the epithelial defects among the 3 groups. BM-MSC- and AT-MSC-transplanted groups showed higher number of corneal and limbal epithelial layers, less disorganization of the stroma, fewer inflammatory cells in the corneal stroma, and fewer goblet cells in the limbal or corneal epithelium than the untreated group.

Conclusions : Transplantation of both BM-MSC and AT-MSC in a LSCD rabbit model reduced the development of corneal opacity, and partially restored the damaged limbal and corneal tissue structure. BM-MSC showed superior efficacy in reducing corneal development of neovascularization whereas AT-MSC better prevented conjunctival invasion. Both types of MSC seem valid alternatives for the treatment of LSCD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.