Cellular Therapy Models: Ex Vivo Chimera Model by Cell Fusion

Cell fusion is a ubiquitous process fundamental to physiological and pathophysiological events common to multiple cell types and species. Performed ex vivo, cell fusion is a versatile research and therapeutic tool for gene mapping, antibody production, discovering new mechanisms in biological processes, inventing alternative therapies for cell reprogramming, restoring organ function, and creating cellular therapeutics for cancer treatment. Cell fusion can be successfully applied by creating cellular therapeutic of donor – recipient chimeric cell (DRCC) in the field of solid organ and vascularized composite allotransplantation (VCA). Immunomodulatory DRCC therapy has the potential to reduce or even eliminate the need for toxic, life-long immunosuppression and to prevent both acute and chronic rejection. This innovative VCA treatment is a combination of ex vivo created chimeric cell therapy with a short-term selective protocol of monoclonal antibody and Cyclosporine A. The utilization of short-term immunosuppressive protocol will provide the opportunity for chimeric cell engraftment, proliferation, and re-education of recipient’s immune system resulting in prolongation of allograft survival. The use of chimeric cells, as a supportive treatment for VCA, would improve the conditions of severely disfigured patients by offering safe alternative approach and providing better functional and aesthetic results compared to standard reconstructive procedures. This chapter summarizes the phenomenon, current discoveries, and advancements in the field of cell fusion, as well as introduces ex vivo creation of chimeric cells and presents potential benefits of chimeric cell-based protocols. Successful application of chimeric cell protocol in VCA experimental models will advance the field of reconstructive transplantation towards clinical trials.