Animal models for basic and translational research in reconstructive transplantation

Abstract

Reconstructive transplantation represents a bona fide option for select patients with devastating tissue loss, which could better restore the appearance, anatomy, and function than any other conventional treatment currently available. Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the potential side effects of chronic multidrug immunosuppression. Thus, any reconstructive measures to improve these non-life-threatening conditions must address a delicate balance of risks and benefits. Today, several exciting novel therapeutic strategies, such as the implementation of cellular therapies including bone marrow or stem cells that integrate the concepts of immune regulation with those of nerve regeneration, are on the horizon. The development of reliable and reproducible small and large animal models is essential for the study of the unique immunological and biological aspects of vascularized composite allografts and to translate such novel immunoregulatory and tolerance-inducing strategies and therapeutic concepts from the bench to bedside. This review provides an overview of the multitude of small and large animal models that have been particularly designed for basic and translational research related to reconstructive transplantation.

Preclinical Models in Vascularized Composite Allotransplantation

“…Clinical measurements of function include the use of video gait kinematics, the Tarlov scale and electromyography, and these have been adopted for pre-clinical models. However, measuring grip strength in NHPs has been a formidable challenge [45]. Orthotopic transplantations in face transplant research have been limited to mandibular segments in rabbits and NHPs [18,29] and a combination of nerve conduction studies of sensory and motor nerve regeneration combined with clinical analysis of functional recovery has been optimal.…”

“…The dog leukocyte antigen (DLA) system has also been well characterised due to its lengthy involvement in transplant research, however their use in preclinical studies is declining. Swine and NHPs are typically inbred and have less mature immune systems, however swine leukocyte antigen (SLA)-typed animals are now available and offer the opportunity to test immunologic interventions in a wellcontrolled environment [45]. It is mandatory that immunologic differences between animals in study groups can be defined to enable the impact of experimental interventions to be accurately established.…”

Skin Allograft and Vascularized Composite Allograft

“…It is thought that such allografts represent a continuous source of donor-derived stem cells that may manipulate the host response and develop immune tolerance through hematopoietic stem cell chimerism. [60][61][62] Chimersim is believed to occur through one of two process: 1) Macrochimerism -the additional donation and receipt of bone marrow from the original allotransplantation donor or 2) Microchimersim -the migration of leukocytes from the transplanted allograft and interaction with recipient leukocytes that result in donor specific tolerance. 63,64 Multiple studies have examined the effect of concomittant VCA and donor bone marrow cell transplant on allograft survival.…”

Minimizing immunosuppression in hand transplantation

“…demonstrated in animal models to favorably modulate the host immune response [51]. In such experimental settings, induction of donor-specific tolerance was attributed to the BM component and to specific immunomodulatory protocols (myeloablative and nonmyeloablative strategies) permissive for BM engraftment [23].…”