Abstract
BackgroundHand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively.MethodsThe immune response elicited upon transplantation of a syngeneic versus allogeneic vascularized groin flap was compared at Post-operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene and protein analyses using quantitative real-time PCR and Multiplex respectively.ResultsImmune cell infiltration began at the donor-recipient interface and paralleled expression of a large group of wound healing-associated genes in both allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread over the entire allograft but remained confined to the wound site in the syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response.ConclusionsHigh resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe also, for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage rejection. We speculate that the highly inflammatory setting created by the unique surgical damage during VCA may enhance acute allograft rejection.
Highlights
Vascularized composite allotransplantation (VCA) is the single-piece transfer of a composite tissue that may include skin, muscle, bone, blood vessels and nerves
This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response
High resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage
Summary
Vascularized composite allotransplantation (VCA) is the single-piece transfer of a composite tissue that may include skin, muscle, bone, blood vessels and nerves. It has the potential to revolutionize the field of reconstructive surgery, by providing a perfect "replacement part” for tissues compromised by disease or trauma It is the only procedure, far, that bears the potential to restore near-normal appearance in patients with socially crippling facial injuries, and offers the most complete functional restoration currently available for hand amputees. To other foreign grafts, VCA grafts are rejected by the recipient’s immune system unless a strict immunosuppressive regimen is given to the recipients throughout their life, often leading to severe side effects [10, 11] Both face and hand transplantations inflict far more surgical damage to both the recipient and donor tissue as compared to transplantation of internal organs resulting in larger surface area of disrupted and damaged tissue. This may partly explain the rate of acute graft rejections within the first year of such transplantations, which is 85% in hand transplantations and 84% in face transplantations, higher than any other field of transplantation [12,13,14,15]
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