Small Animal Models of Xenotransplantation

Abstract

Organ transplantation has become a successful and acceptable treatment for end-stage organ failure. Such success has allowed transplant patients to resume a normal lifestyle. The demands for transplantation have been steadily increasing, as more patients and new diseases are being deemed eligible for treatment via transplantation. However, it is clear that human organs will never meet the increasing demand of transplantation. Therefore, scientists must continue to pursue alternative therapies and explore new treatments to meet the growing demand for the limited number of organs available. Transplanting organs from animals into humans (xenotransplantation) is one such therapy. The observed enthusiasm for xenotransplantation, irrespective of the severe shortage of human organs and tissues available for transplantation, can be said to stem from at least two factors. First, there is the possibility that animal organs and tissues might be less susceptible than those of humans to the recurrence of disease processes. Second, a xenograft might be used as a vehicle for introducing novel genes or biochemical processes which could be of therapeutic value for the transplant recipient.To date, millions of lives have been saved by organ transplantation. These remarkable achievements would have been impossible without experimental transplantation research in animal models. Presently, more than 95% of organ transplantation research projects are carried out using rodents, such as rats and mice. The key factor to ensure the success of these experiments lies in state-of-the art experimental surgery. Small animal models offer unique advantages for the mechanistic study of xenotransplantation rejection. Currently, multiple models have been developed for investigating the different stages of immunological barriers in xenotransplantation. In this chapter, we describe six valuable small animal models that have been used in xenotransplantation research. The methodology for the small animal model establishment includes animal selection, preoperative care, anesthesia, postoperative care, and detailed procedures.

A new method for skin grafting in murine model

“…Despite some interspecies differences between the immunology of rodents and humans, these models have provided invaluable information regarding the biology of allo‐transplantation. Moreover, the use of well‐established animal models provides the opportunity to incorporate the protocols and information from the large body of previous research …”

Orthotopic Kidney Transplantation in Mice: Technique Using Cuff for Renal Vein Anastomosis

“…The murine kidney is extremely sensitive to ischemia/reperfusion injury, and to perform a successful operation the secondary warm ischemic time should be less than 35 minutes [9,10]. As described by Martins, kidney transplantation in these settings is challenging, and the success rates of even experienced surgeons vary between 40 and 70% [11,12].…”

“…Anastomotic stenosis, bleeding, and thrombosis are severe complications causing subsequent graft failure secondary to technical problems [9]. Therefore, the construction of high quality and reproducible anastomoses plays a key role in achieving good graft survival and therefore further experimental results.…”

Xenotransplantation: Current Status in Preclinical Research

“…Xenotransplantation has a long history with a number of animal models, including mouse, rat, and NHP, and has been used to reveal the mechanisms of rejection responses (156,157). Old World NHPs are the preferred surrogate for humans in exploring the response to pig xenograft transplantation because of their immunological similarities to humans (6).…”