Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials

Abstract

Purpose: Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors.

Recent findings: Advances in gene editing technology have allowed for the efficient production of multi-transgenic porcine donors leading improved xenograft survival in baboons, up to 2-years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above.

Summary: Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.

Figure 1

(A) Preparation of thymokidney (TK) in a juvenile GalTKO pig and transplantation of a GalTKO TK in a baboon. (B) A transplanted GalTKO vascularized thymic lobe graft (VTL) in a baboon.

Figure 2

PCMV induced the early loss of life-supporting kidneys. (Left bottom) A life-supporting TK graft from a pCMV negative donor (>60 days). (Right bottom) Rejected TKs from pCMV+ donors.