Engineering Strategies for Allogeneic Solid Tissue Acceptance

Abstract

Systemic immunosuppressants have allowed the transplantation of life-saving organs. However, they cause deleterious effects and long-term graft failure. Strategies promoting allogeneic graft acceptance and the maintenance of immunological competence have been proposed.Cell-based tolerance-inducing strategies that preserve immune competence have already extended human allograft acceptance, although toxic side effects or difficult reproduction of observed effects in humans have counteracted their clinical translation.Localized tolerance/immunosuppression mediated through bioengineered setups comprising immunomodulatory biomaterials and/or tissue engineeringinspired tools already achieved allograft acceptance in murine models and are game changing in the field. Such advances have contributed to unveiling the complex interplay of immune cells and allogeneic transplants.

The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles

“…For GVHD, full hematopoietic chimerism has been suggested amongst different strategies for the recipient's response to allograft acceptance. In contrast, tolerogenic leukocytes, apoptotic donor leukocytes, mesenchymal stem cells, costimulation blockade, and immunization have shown no or minimal risk 66 …”

“…However, because mixed chimerism caused tolerance to human kidney allografts but not to pancreatic islet, lung, or heart allografts, the efficacy of chimerism in avoiding allograft rejection appears to be tissue‐type dependent 71 . Despite lowering the risk of GVHD and retaining immunological competence, permanent mixed chimeras appear only to prevent rejection in HLA‐matched allograft recipients, and the efficiency of transitory mixed chimeras in inducing tolerance varies across recipients 66 . Similar to chimerism, tolerogenic leukocyte research focuses on kidney and liver transplants.…”

“…In contrast, tolerogenic leukocytes, apoptotic donor leukocytes, mesenchymal stem cells, costimulation blockade, and immunization have shown no or minimal risk. 66 Cell therapy is becoming increasingly popular as an alternative to conventional drug therapy for treating allograft rejection. 67,68 Hematopoietic chimerism is one of the most effective methods for inducing tolerance to donor-derived tissue and organ grafts without using immunosuppressive drugs; here, the host's bone marrow is completely replaced by a donor bone marrow to create a full chimera.…”

“…71 Despite lowering the risk of GVHD and retaining immunological competence, permanent mixed chimeras appear only to prevent rejection in HLA-matched allograft recipients, and the efficiency of transitory mixed chimeras in inducing tolerance varies across recipients. 66 Similar to chimerism, tolerogenic leukocyte research focuses on kidney and liver transplants. Although autologous cell sources are favored, their suppressive capacity varies.…”

Dual‐Targeting Nanovesicles Carrying CSF1/CD47 Identified from Single‐Cell Transcriptomics of Innate Immune Cells in Heart Transplant for Alleviating Acute Rejection

“…Although survival rates have improved due to optimized surgical methods, advanced organ acquisition, and medical therapy, immune rejection is still the main cause of organ transplantation failure. [1,2] Immunosuppressive drugs currently used clinically are mainly targeted adaptive immunity T cells, including the classic "Calcineurin-NFAT" T cell activation pathway and the mTOR metabolic pathway related to T cell growth and proliferation. [3,4] The long-term use of these drugs, however, can cause serious liver and kidney toxicity and even trigger leukemia.…”