Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Purpose: Unlike solid organ transplantation, VCA relies on adequate nerve regeneration for graft function. There is a lack of understanding regarding how the alloimmune response affects nerve regeneration in the setting of VCA. Here we compare nerve regeneration in allogeneic and syngeneic limb transplantion, with and without Cyclosporine (CsA) treatment. We hypothesize that rejection of donor Schwann cells (SCs) within limb allografts is detrimental to nerve regeneration and will impede muscle reinnervation.
Methods: Three groups of rats(n=6) received either syngeneic orthotopic hindlimbs (SYN) without treatment; syngeneic hindlimbs treated with CsA (SYN+CsA); or limb allografts treated with CsA (ALLO+CsA). Graft rejection was monitored histologically and grossly. At 5 weeks, nerve regeneration was assessed by non-biased quantitative nerve histomorphometry. Caspase 3 and IL-6 were measured by RT-PCR. At 8 weeks, motor enplate reinnervation was assessed with neuromuscular junction staining. Immunohistochemical assessement of cellular infiltrate and SC rejection as well as multiplex cytokine analysis was also performed.
Results: No evidence of acute graft rejection, grossly or histologically, was found in any of the three study groups sacrificed at 5 weeks. The following significant statistical differences (p<0.05) were found in total number of nerve fibers: SYN+CsA (10959.3 ± 1132.6) > ALLO+CsA (9096.8 ± 1613.8) > SYN (68997 ± 1380.3). Groups treated with CsA showed greater nerve fiber width (uM) than the untreated isografts (p<0.05):SYN+CsA (3.19 ± 0.17), ALLO+CsA (3.42 ± 0.60) >SYN (2.86 ± 0.12). RT-PCR data for markers of cellular rejection and neural inflammation indicate initial trends towards greater Caspase 3 and IL-6 in ALLO+CsA as compared to SYN+CsA.
Conclusions: (1) CsA enhanced nerve regeneration in VCA by a mechanism that goes beyond prevention of graft rejection (SYN+CsA>SYN). (2) A syngeneic VCA provided a more favorable environment for nerve regeneration than an allogeneic graft (SYN+CsA>ALLO+CsA). This may be due to subacute rejection of allogeneic SCs. This study highlights the importance of considering the effects of immunosuppression and rejection on nerve regeneration when developing novel treatment protocols in VCA.
To cite this abstract in AMA style:Tuffaha S, Budihardjo J, Afrooz P, Sarhane K, Jindal R, Cooney D, Brandacher G, Lee W. Effects of the Allo-Immune Response On Nerve Regeneration in Vascularized Composite Allotranplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/effects-of-the-allo-immune-response-on-nerve-regeneration-in-vascularized-composite-allotranplantation/. Accessed July 19, 2018.
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