Local immunоcorrection with MMSC-like limbal cells in high-risk keratoplasty patients

Background. Local immunosuppressive therapy resistance in over that 45% of recipients in high-risk keratoplasty determines search for the new methods of immune reaction suppression by activation of physiological tolerance mechanisms based on the cell technologies. With this in view mesenchymal stem/progenitor limbal cells with phenotype and properties of bone marrow MMSCs are of great interest as they form an outer cell-tissue niche of the eyeball, accomplish local immunity regulation, physiological and reparative corneal regeneration. Purpose. To evaluate cadaveric donor graft survival rate in high-risk recipients by co-transplantation of pre-cultured allogenic limbal transplants. Materials and methods. As a first step limbal transplants taken from the cadaver eye were cultured for 25,0±3,0 days in the medium (Borzenok-Moroz). Functional activity of the cells was monitored by the content of pro- and anti-inflammatory cytokines in the culture medium by ELISA. Phenotype of the cells after culturing was determined by flow cytometry with a panel of antibodies to MMSCs. At the second (clinical) step penetrating keratoplasties were carried out in 69 high-risk patients. Experimental group (1st) comprised of 36 patients whom cultured limbal cells and cadaver corneas were transplanted simultaneously. In the 2nd (control) group (n=33) standard penetrating keratoplasty was performed. Results. The results of observation during the first 12 months after the surgery showed that in the 1st group transplant survival rate was much higher than in the 2nd group, 31 recipient (86,1%) and 23 recipient (69,7%), respectively. Endothelial cell loss was also much higher in the control group as opposed to the experimental group, 23,8±1,4% and 14,1±0,57%, respectively. Conclusion. Limbal transplants preserve their viability, demonstrate immune-regulatory activity, and contribute to reprogramming of pro-inflammatory to anti-inflammatory local immune response after keratoplasty. Inhibition of local immune reactions by limbal cells co-transplantation contributes to long-term survival rate of the corneal grafts and preserved endothelial cells. [PUBLICATION ABSTRACT]