Xenotransplantation model for vascularized musculoskeletal tissues in rodents

Abstract

The purpose of this study was to establish a model and to define the mechanism of rejection for the transplantation of vascularized musculoskeletal xenografts between C57BL/6j (B6) mice and Lewis rats. This was accomplished by using conventional skin xenografts to determine immunologic baseline data between these species and by performing musculoskeletal grafts from the B6 mice transplanted into Lewis rats. After the transplant, the xenografts were examined histologically and the recipients were assessed for immune reaction using in vitro assays to measure both cell-mediated and humoral responses. The results obtained from the skin xenografts showed activation of both cellular and humoral immunologic responses. All musculoskeletal xenografts were rejected between 3 and 4 postoperative days. Histologically, the grafts showed extensive vascular injury manifested by thrombosis and hemorrhage, suggesting an early humoral response. Anti-donor antibody production was detected in the recipient's sera soon after rejection of the xenogeneic tissue. The cell-mediated immune response, although detectable by the in vitro assays, was less pronounced than the humoral response and corroborated the histologic findings of mild lymphocyte infiltration in the rejected tissue. These results demonstrate that humoral rejection plays a predominant role in the rejection of vascularized musculoskeletal xenotransplants between concordant species. This mouse-to-rat vascularized xenograft model will be utilized for further studies on inducing tolerance to vascularized musculoskeletal xenografts.

Surgical angiogenesis: a new approach to maintain osseous viability in xenotransplantation

“…Certainly, major unsolved problems remain, including risk of xenozoonoses like porcine endogenous retroviruses, and serious immune rejection [24]. This includes the potentially devastating complement mediated hyperacute rejection in discordant species [22,24–27] and a vigorous acute vascular rejection , that is histologically similar to hyperacute rejection but that occurs within days or weeks [22,28–30]. Other immunological reactions in xenotransplantation include cellular and chronic rejection.…”

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

“…Instead, acute cellular rejection occurs, which is similar to allograft rejection (Calne, 1970; Elwood et al, 1998; Najarian, 2003; Sachs et al, 2001). Although organ xenotransplantation is not a new science, there are only a few studies about vascularized composite xenotransplantation (Hebebrand et al, 1998; Tanabe et al, 2000). Thus, we hypothesized that xeno‐preservation (using xenotransplantation for tissue preservation) might be used to preserve vascularized composite tissues beyond 24 h, and transplantation of xeno‐preserved VCA would be possible without any significant immunologic drawbacks.…”