Open AccessTherapeutic Effect of Human Adipose Tissue‐Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage
Author(s) -
Galindo Sara,
Herreras José M.,
LópezPaniagua Marina,
Rey Esther,
de la Mata Ana,
PlataCordero María,
Calonge Margarita,
NietoMiguel Teresa
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2672
Subject(s) - mesenchymal stem cell , stem cell , biology , corneal epithelium , limbal stem cell , transplantation , adipose tissue , adult stem cell , cornea , stem cell marker , immunology , stem cell transplantation for articular cartilage repair , pathology , microbiology and biotechnology , endothelial stem cell , medicine , surgery , in vitro , neuroscience , biochemistry , endocrinology
Abstract 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