Engineering Strategies for Allogeneic Solid Tissue Acceptance

abstract

Advances in allogeneic transplantation of solid organs and tissues depend on our understanding of mechanisms that mediate the prevention of graft rejection. For the past decades, clinical practice has established guidelines to prevent allograft rejection, which mostly rely on the intake of nontargeted immunosuppressants as the gold standard. However, such lifelong regimens have been reported to trigger severe morbidities and commonly fail in preventing late allograft loss. In this review, the biology of allogeneic rejection and self-tolerance is analyzed, as well as the mechanisms of cellular-based therapeutics driving suppression and/or tolerance. Bioinspired engineering strategies that take advantage of cells, biomaterials, or combinations thereof to prevent allograft rejection are addressed, as well as biological mechanisms that drive their efficacy.

keywords

BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; MIXED HEMATOPOIETIC CHIMERISM; RENAL-ALLOGRAFT TOLERANCE; DONOR-SPECIFIC TOLERANCE; KIDNEY-TRANSPLANTATION; MONOCLONAL-ANTIBODY; NONHUMAN-PRIMATES; IMMUNE TOLERANCE; SURVIVAL

subject category

Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental

authors

Sousa, AR; Mano, JF; Oliveira, MB

our authors

acknowledgements

This work was supported by the Programa Operacional Competitividade e Internacionalizacao, in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects `TranSphera' (PTDC/BTM-ORG/30770/2017). This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. M.B.O. acknowledges the individual contract CEECIND/03605/2017. A.R.S. acknowledges the PhD grant SFRH/BD/145765/2019.

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