title: Human Bone Marrow Stromal Cells Differentiate Into Corneal Tissue and Prevent Ocular Graft-Versus-Host Disease in Mice.
abstract: Clinical trials have assessed the use of human bone marrow stromal cells (hBMSCs) for the treatment of immune-related disorders such as graft-versus-host disease (GVHD). In the current study, we show that GFP(+)-transduced hBMSCs generated from bone marrow migrate and differentiate into corneal tissue after subconjunctival injection in mice. Interestingly, these hBMSCs display morphological features of epithelial, stromal, and endothelial cells and appear at different layers and with different morphologies depending on their position within the epithelium. Furthermore, these cells display ultrastructural properties, such as bundles of intermediate filaments, interdigitations, and desmosomes with GFP(-) cells, which confirms their differentiation into corneal tissues. GFP(+)-transduced hBMSCs were injected at different time points into the right eye of lethally irradiated mice undergoing bone marrow transplantation, which developed ocular GVHD (oGVHD). Remarkably, hBMSCs massively migrate to corneal tissues after subconjunctival injection. Both macroscopic and histopathological examination showed minimal or no evidence of GVHD in the right eye, while the left eye, where no hBMSCs were injected, displayed features of GVHD. Thus, in the current study, we confirm that hBMSCs may induce their therapeutic effect at least in part by differentiation and regeneration of damaged tissues in the host. Our results provide experimental evidence that hBMSCs represent a potential cellular therapy to attenuate oGVHD.
authors.affiliation: Department of Hematology, University Hospital Virgen del Rocío/IBIS/CSIC/University of Seville, Seville, Spain.
authors.forename: Luis Ignacio
authors.initials: LI
authors.lastname: Sánchez-Abarca
authors.forename: Emiliano
authors.initials: E
authors.lastname: Hernández-Galilea
authors.forename: Rebeca
authors.initials: R
authors.lastname: Lorenzo
authors.forename: Carmen
authors.initials: C
authors.lastname: Herrero
authors.forename: Almudena
authors.initials: A
authors.lastname: Velasco
authors.forename: Soraya
authors.initials: S
authors.lastname: Carrancio
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero-Velázquez
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Rodríguez-Barbosa
authors.forename: Marta
authors.initials: M
authors.lastname: Parrilla
authors.forename: Consuelo
authors.initials: C
authors.lastname: Del Cañizo
authors.forename: Jesús
authors.initials: J
authors.lastname: San Miguel
authors.forename: José
authors.initials: J
authors.lastname: Aijón
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Pérez-Simón
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003315:Cornea / Q000166:cytology*; D016039:Corneal Transplantation / Q000009:adverse effects*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control* / Q000628:therapy; D049452:Green Fluorescent Proteins; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged
chemical_list: D016326:Extracellular Matrix Proteins; D049452:Green Fluorescent Proteins