Evolution of the rat hind limb transplant as an experimental model of vascularized composite allotransplantation: Approaches and advantages

Abstract

As clinical experience with surgical techniques and immunosuppression in vascularized composite allotransplantation recipients has accumulated, vascularized composite allotransplantation for hand and face have become standard of care in some countries for select patients who have experienced catastrophic tissue loss. Experience to date suggests that clinical vascularized composite allotransplantation grafts undergo the same processes of allograft rejection as solid organ grafts. Nonetheless, there are some distinct differences, especially with respect to the immunologic influence of the skin and how the graft is affected by environmental and traumatic insults. Understanding the mechanisms around these similarities and differences has the potential to not only improve vascularized composite allotransplantation outcomes but also outcomes for all types of transplants and to contribute to our understanding of how complex systems of immunity and function work together. A distinct disadvantage in the study of upper extremity vascularized composite allotransplantation recipients is the low number of clinical transplants performed each year. As upper extremity transplantation is a quality of life rather than a lifesaving transplant, these numbers are not likely to increase significantly until the risks of systemic immunosuppression can be reduced. As such, experimental models of vascularized composite allotransplantation are essential to test hypotheses regarding unique characteristics of graft rejection and acceptance of vascularized composite allotransplantation allografts. Rat hind limb vascularized composite allotransplantation models have been widely used to address these questions and provide essential proof-of-concept findings which can then be extended to other experimental models, including mice and large animal models, as new concepts are translated to the clinic. Here, we review the large body of rat hind limb vascularized composite allotransplantation models in the literature, with a focus on the various surgical models that have been developed, contrasting the characteristics of the specific model and how they have been applied. We hope that this review will assist other researchers in choosing the most appropriate rat hind limb transplantation model for their scientific interests.

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

“…Rat limb VCA has emerged as a model that has been used to study allograft rejection [6], novel induction protocols [7], and studies to prolong graft preservation [8][9][10][11]. These studies have predominately focused on hindlimb VCAs [12]. However, forelimbs are of higher clinical interest in reconstructive transplantation [13][14][15][16] since the majority of clinical VCA cases are upper extremity and hand transplants.…”

Successful Extension of Vascularized Composite Allograft Perfusion Cold Storage to 24 h in a Rat Hindlimb Transplant Model

“…1 VCAs serve as potential replacements for traumatic tissue loss, including limb injuries and limb losses from explosive devices in the battlefield. [2][3][4][5][6] Clinical applications of VCA transplantation allow for the reconstruction and replacement of damaged or lost tissue with the same tissue from a suitable donor. 7 VCA transplantation is not considered a lifesaving procedure; however, it serves to improve patient quality of life and is thus labeled a life-enhancing operation.…”