Estudio Del Efecto De Las Células Madre Mesenquimales Sobre El Segmento Anterior Del Ojo En Un Modelo Experimental De Enfermedad De Injerto Contra Huésped Ocular

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Introduction: Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality among patients undergoing allogeneic hematopoetic stem cell transplantation. Ocular involvement has been reported in 40-90% of patients. Physiopathology of ocular graft-versus-host disease (oGVHD) is not well understood, dry eye is the main complication. Current treatments are limited and ineffective. Considering the immunomodulatory effect of mesenchymal stem cells (MSC) and their potential role to regenerate damaged tissues, could be useful in the oGVHD treatment. Objectives: To establish a murine model of GVHD. To evaluate distribution, characterization and the feasibility of human CSM differentiation after subconjunctival injection in healthy mice and oGVHD murine model. Methods: BALB/c (H2d) mice were used as recipients in the GVHD model, they received total body irradiation and an intravenous infusion of C57BL/6 allogeneic donor bone marrow cells with splenocytes. The degree of oGVHD was assessed by a scoring system. We analyzed the histopathologic features of GVHD present in eyes. Human MSC were isolated from bone marrow cells of healthy donors. We administered a subconjunctival injection of MSC in mice. We carried out Western-blot, immunohistochemistry and electron microscope analysis. Results: All mice receiving donor splenocytes exhibited clinical and histopathological features of GVHD at lids, lachrymal gland, conjunctiva, cornea and limbus. MSC are distributed across the mouse cornea and limbus after subconjuntival injection and acquire in vivo ultrastructural features of each layer. We found that MSC migrate to cornea and differentiate into corneal cells, which is strikingly more evident in mice with oGVHD. Conclusions: The current study establishes an animal model for the evaluation of oGVHD. The ocular surface is a GVHD target organ. Subconjunctival injected MSC were able to migrate into cornea and limbus. MSC are capable of differentiating into corneal…