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Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue‐derived mesenchymal stem cells (hAT‐MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT‐MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E‐cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT‐MSC transplantation. For the first time, we demonstrated that hAT‐MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT‐MSCs as a novel treatment of ocular surface failure due to LSCD. hAT‐MSCs represent an available, non‐immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. S tem  C ells   2017;35:2160–2174

Therapeutic Effect of Human Adipose Tissue‐Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage