Abstract
Reconstructive transplantation, also referred to as vascularized composite allotransplantation (VCA), has rapidly emerged as a viable approach to repairing complex tissue defects. Over the past 20 years, major advances have been made in the field of VCA allowing for successful transplantation of over 150 hand/forearm/arm, larynx, trachea, abdominal wall, vascularized knee, and facial transplants with encouraging outcomes. These innovations have currently outpaced the scientific community’s ability to fully address certain immunological and clinical challenges. The literature on ischemia-reperfusion injury (IRI) in VCA is limited and mechanistic questions remain. Specifically, the role IRI may play in acute rejection, the progression towards chronic rejection, or immune regulation and tolerance induction has only been partially or indirectly addressed. Hence, much of what we understand regarding IRI in VCA is extrapolated from research in solid organ transplantation (SOT). This review will address the role of IRI in VCA, first outlining its impact on SOT, it’s effects on the immune system and allograft rejection, as well as the clinical implications that IRI has for VCA outcomes.
Highlights
Reconstructive transplantation, referred to as vascularized composite allotransplantation (VCA), has rapidly emerged as a viable approach to repairing complex tissue defects
ischemia-reperfusion injury (IRI) poses a unique challenge for the transplant surgeon, as some period of ischemia is unavoidable given the nature of the procedure
It has been shown that IRI leads to increased expression of MHC antigens and activates the innate immune system producing inflammation, leading to acute rejection, hastens the development of chronic rejection, and impaired chances for immune regulation and tolerance induction [5]
Summary
The literature in SOT has clearly demonstrated that IRI is a potent activator of the immune system and subsequently leads to poor functional outcomes [1,2,3,4]. Studies have shown that prolonged ischemia in transplanted hearts leads to increased entry of activated T cells and binding of natural IgM antibodies to self-antigens exposed after tissue ischemia [8,9]. The former leads to leukocyte migration and accumulation in peripheral tissues and the latter is a potent activator of the complement cascade. Analysis of over 6,000 kidney transplant recipients showed that patients with prolonged ischemic times suffered early acute rejection and decreased 6-year renal graft survival [13] These findings were independent of donor/recipient age, HLA mismatch, reactive antibodies, and early rejection treatments. It is possible that vascularized composite allografts may be even more susceptible to IRI given the diversity of tissue components contained within the graft [16]
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