Induction of tolerance to allogeneic transplant using the strategy of mixed hematopoietic chimerism: studies in large animal models

The review presents the collected material on the induction of tolerance to allografts in large animal models (pigs and non-human primates) in preclinical studies. Since progress in clinical transplantology is impossible without the use of step-by-step studies in preclinical models on large animals, experiments on these models are still relevant. The technique of tolerance induction described in this review involves the formation of chimerism in recipients after hematopoietic stem cell transplantation based on the in vivo removal of newly formed donor-reactive T lymphocytes during their interaction in the thymus with donor antigen-presenting cells, with parallel development of tolerance to the organ transplanted from the same donor. The presented data demonstrate that hematopoietic stem cell transplantation is a real alternative to lifelong use of immunosuppressive drugs. It is necessary to continue research in order to understand the immunological mechanisms underlying tolerance based on mixed chimerism in order to use potential targets and necessary manipulations for future strategies of tolerance induction. Knowledge gained from large animal models may have direct implications for various human donor transplant and will greatly enhance the implementation of tolerance induction protocols to prevent rejection of donor organs and tissue assemblies. © 2025 Elsevier B.V., All rights reserved.