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.

Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy

“…They fulfil a function as a reservoir of undifferentiated cells for the regeneration of the tissues where they are located, having been isolated in diverse adult or extraembryonic tissues [ 53 , 54 ]. They present the migration and homing capacity to the site of the lesion in response to the cytokines, chemokines, and growth factors released [ 55 , 56 ]. In addition, they do not raise ethical issues and have very low tumorigenesis potential [ 57 , 58 , 59 , 60 ].…”

“…Different mesenchymal stem-like cell populations have been identified in the eye: basal limbus, corneal stroma, trabecular meshwork, choroids, and periorbital fat [ 47 , 61 , 62 ]. MSCs can differentiate both towards mesenchymal lineages and other germ lines [ 58 , 59 ], among them different cell types present in the corneal surface such as epithelial, stromal, and endothelial [ 55 , 60 , 63 ].…”

“…As discussed above, many of the MSCs’ action mechanisms are carried out through the release of a wide variety of bioactive substances encompassed under the concept of the secretome [ 56 , 66 , 70 ]. The secretome is composed of soluble factors and extracellular vesicles, as microvesicles or exosomes [ 55 , 69 ]. It is thought to be encoded by approximately 10% of the human genome [ 91 , 92 ].…”

Estudio de la capacidad terapéutica de las células mesenquimales administradas por vía subconjuntival en el tratamiento de la enfermedad injerto contra receptor ocular en un modelo murino optimizado

“…Las hCSM inyectadas contribuyen a la recuperación funcional e histológica de la superficie ocular de los animales tratados (Sánchez-Abarca y cols. 225 ). En este estudio se describieron los cambios anatomopatológicos de la superficie ocular en el modelo murino de EICRo.…”

“…Las hCSM inyectadas por vía subconjuntival contribuyen a la recuperación funcional e histológica de la superficie ocular de los animales con EICRo tratados 225 .…”