Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome

• Published in: PloS one Vol. 10; no. 3; p. e0117945
• Main Authors: Fuentes-Julián, Sherezade, Arnalich-Montiel, Francisco, Jaumandreu, Laia, Leal, Marina, Casado, Alfonso, García-Tuñon, Ignacio, Hernández-Jiménez, Enrique, López-Collazo, Eduardo, De Miguel, Maria P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02-03-2015; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Adipose Tissue - cytology; Allografts; Analysis; Animal models; Animals; Antigens; Cell Differentiation; Cell survival; Coculture Techniques; Cornea; Cornea - pathology; Corneal Diseases - pathology; Corneal Diseases - therapy; Corneal Transplantation; Cytokines - metabolism; Dendritic cells; Ecological risk assessment; Edema; Female; Graft rejection; Graft Survival - physiology; Grafting; Grafts; Humans; Immune privilege; Immunohistochemistry; Immunology; Immunosuppression; Infiltration; Inflammation; Injection; Laboratories; Leukocytes; Lymphocytes; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Rabbits; Rejection; Risk; Skin & tissue grafts; Stem cell transplantation; Stem cells; Surgery; Survival; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transplantation, Heterologous; Transplantation, Homologous; Transplants; Transplants & implants; Vascularization; New Zealand; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117945

The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice.