Decellularization as a prevention of immune response activation to allogeneic pulmonary valves

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Abstract

The top priority of clinical immunology is the study of alloreactivity mechanisms and development of methods for prevention of transplanted organs rejection. The discharge of vascular and valvular prostheses from a non-functional cellular debris is effective way to reduce their immunogenicity in the post-transplant period and to extend their functional usefulness. Obviously, removal of the maximum amount of HLA-determinants in cell membranes using decellularization should lead to reduction of complication after heart valves allogeneic transplantation. However, the key mechanisms of the immune response during acellular biomatrix implantation are insufficiently studied. In this study we investigated the influence of preimplantation treatment of human cardiac valves on the in vitro expression of important lymphocytes regulators CD28 and CD152 (CTLA-4). We found a significant rise expression of CD8+28+ from 37,9% to 44,5%, CD8+152+ from 0,3% to 22,6%, CD4+28+ from 96,4% to 98,4% and CD4+152+ from 0,04% to 43,8%, p<0,05 on lymphocytes after cultivation with native valves fragments and valves after cryopreservation, that indicated T-cells activation in the presence of cellular antigens. In contrast, no difference was found in the quantitative expression of CD28 and CD152 on T-lymphocytes after culturing with decellularized valves in comparison with the control, that indicating the absence of T-cell response to allogeneic acellular tissue matrix of the heart valves. Thus, from the point of applied immunology was shown that transplantation of decellularized allogeneic valve is preferable in comparison with native and cryopreserved grafts. Also identified candidate molecules of the transplantation immunity represent a possible therapeutic interest.

About the authors

D. S Sergeevichev

E.N. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Novosibirsk

V. V Sergeevicheva

Research Institute of Clinical Immunology, SB of the RAMS, Novosibirsk

A. I Subbotovskaya

E.N. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Novosibirsk

M. B Vasilyeva

E.N. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Novosibirsk

A. A Dokuchayeva

E.N. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Novosibirsk

A. M Karaskov

E.N. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Novosibirsk

V. A Kozlov

Research Institute of Clinical Immunology, SB of the RAMS, Novosibirsk

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