title: A modified heterotopic swine hind limb transplant model for translational vascularized composite allotransplantation (VCA) research.
abstract: Vascularized Composite Allotransplantation (VCA) such as hand and face transplants represent a viable treatment option for complex musculoskeletal trauma and devastating tissue loss. Despite favorable and highly encouraging early and intermediate functional outcomes, rejection of the highly immunogenic skin component of a VCA and potential adverse effects of chronic multi-drug immunosuppression continue to hamper widespread clinical application of VCA. Therefore, research in this novel field needs to focus on translational studies related to unique immunologic features of VCA and to develop novel immunomodulatory strategies for immunomodulation and tolerance induction following VCA without the need for long term immunosuppression. This article describes a reliable and reproducible translational large animal model of VCA that is comprised of an osteomyocutaneous flap in a MHC-defined swine heterotopic hind limb allotransplantation. Briefly, a well-vascularized skin paddle is identified in the anteromedial thigh region using near infrared laser angiography. The underlying muscles, knee joint, distal femur, and proximal tibia are harvested on a femoral vascular pedicle. This allograft can be considered both a VCA and a vascularized bone marrow transplant with its unique immune privileged features. The graft is transplanted to a subcutaneous abdominal pocket in the recipient animal with a skin component exteriorized to the dorsolateral region for immune monitoring. Three surgical teams work simultaneously in a well-coordinated manner to reduce anesthesia and ischemia times, thereby improving efficiency of this model and reducing potential confounders in experimental protocols. This model serves as the groundwork for future therapeutic strategies aimed at reducing and potentially eliminating the need for chronic multi-drug immunosuppression in VCA.
authors.affiliation: Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine.
authors.forename: Zuhaib
authors.initials: Z
authors.lastname: Ibrahim
authors.forename: Damon S
authors.initials: DS
authors.lastname: Cooney
authors.forename: Jaimie T
authors.initials: JT
authors.lastname: Shores
authors.forename: Justin M
authors.initials: JM
authors.lastname: Sacks
authors.forename: Eric G
authors.initials: EG
authors.lastname: Wimmers
authors.forename: Steven C
authors.initials: SC
authors.lastname: Bonawitz
authors.forename: Chad
authors.initials: C
authors.lastname: Gordon
authors.forename: Dawn
authors.initials: D
authors.lastname: Ruben
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
authors.forename: Gerald
authors.initials: G
authors.lastname: Brandacher
mesh_terms: D064591:Allografts / Q000098:blood supply; D000818:Animals; D005260:Female; D006614:Hindlimb / Q000098:blood supply* / Q000637:transplantation*; D008297:Male; D023421:Models, Animal; D013552:Swine; D014184:Transplantation, Homologous / Q000379:methods