Human Bone Marrow Stromal Cells Differentiate into Corneal Tissue and Prevent Ocular Graft-Versus-Host Disease in Mice

Cell Transplantation

Article

Jesús San Miguel¹  Marta Parrilla²  José Aijón³  Almudena Velasco³  José Antonio Pérez-Simón⁴  Teresa Caballero-Velázquez⁴  Luis Ignacio Sánchez-Abarca⁵  Soraya Carrancio⁶  Consuelo Del Cañizo⁷  Carmen Herrero⁷  Emiliano Hernández-Galilea⁸  Rebeca Lorenzo⁸  José Ignacio Rodríguez-Barbosa⁹ 

[1] Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain;Department Cell Biology and Pathology, INCyL, University of Salamanca, Salamanca, Spain;Department Cell Biology and Pathology, INCyL, University of Salamanca, Salamanca, Spain;Institute of Biomedicine Investigation of Salamanca (IBSAL), Salamanca, Spain;Department of Hematology, University Hospital Virgen del Rocío/IBIS/CSIC/University of Seville, Seville, Spain;Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;Department of Hematology, University Hospital Virgen del Rocío/IBIS/CSIC/University of Seville, Seville, Spain;Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;Institute of Biomedicine Investigation of Salamanca (IBSAL), Salamanca, Spain;Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;Institute of Biomedicine Investigation of Salamanca (IBSAL), Salamanca, Spain;Department of Surgery, Ophthalmology Service, University Hospital of Salamanca, University of Salamanca, Salamanca, Spain;Institute of Biomedicine Investigation of Salamanca (IBSAL), Salamanca, Spain;Immunobiology Section, Institute of Biomedicine, University of León, León, Spain;

关键词: Human bone marrow stromal cells (hBMSCs);    Ocular graft-versus-host disease (oGVHD);    Cornea;    Subconjunctival injection;    Cell migration;    Differentiation;   

DOI  :  10.3727/096368915X687480

 received in 2014-07-22, accepted in 2015-02-06,  发布年份 2015

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2015 Cognizant Comm. Corp.

【 图 表 】

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