Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome.
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.
Cell Engineering Laboratory, IdiPAZ, La Paz Hospital Research Institute, Madrid, Spain.
Sherezade
S
Fuentes-Julián
Ophthalmology Department, Ramon y Cajal Hospital Research Institute, Madrid, Spain.
Francisco
F
Arnalich-Montiel
Ophthalmology Department, Ramon y Cajal Hospital Research Institute, Madrid, Spain.
Laia
L
Jaumandreu
Ophthalmology Department, Ramon y Cajal Hospital Research Institute, Madrid, Spain.
Marina
M
Leal
Ophthalmology Department, Ramon y Cajal Hospital Research Institute, Madrid, Spain.
Alfonso
A
Casado
Cell Engineering Laboratory, IdiPAZ, La Paz Hospital Research Institute, Madrid, Spain.
Ignacio
I
García-Tuñon
Tumor Immunology Department and Innate Immunity Group, IdiPAZ, Madrid, Spain.
Enrique
E
Hernández-Jiménez
Tumor Immunology Department and Innate Immunity Group, IdiPAZ, Madrid, Spain.
Eduardo
E
López-Collazo
Cell Engineering Laboratory, IdiPAZ, La Paz Hospital Research Institute, Madrid, Spain.
Maria P
MP
De Miguel
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D018920:Coculture Techniques; D003315:Cornea / Q000473:pathology; D003316:Corneal Diseases / Q000473:pathology / Q000628:therapy; D016039:Corneal Transplantation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011817:Rabbits; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D016207:Cytokines