Kidney Xenotransplantation: Are We Ready for Prime Time?

Abstract

Purpose of review: With the exponential increase in interest and great strides toward clinical application, many experts believe we are ready for kidney xenotransplant human trials. In this review, we will examine the obstacles overcome and those yet to be conquered, discussing the human trials performed and the questions they raised. Additionally, we will revisit overlooked aspects that may be crucial for improvements and suggest future approaches for xenotransplant research.

Recent findings: Improving survival in pig-to-non-human-primate models with the identification of an ideal immunosuppression regimen led to 3 cases of kidney xenotransplant in brain-dead humans with limited follow-up and a single clinical case of pig-to-human heart xenotransplant with 2-month survival. With limited human results and unlimited potential, xenotransplantation shines a beacon of hope for a brighter future. However, we must navigate through the complexities of balancing scientific progress and patient welfare, avoiding being blinded by xenotransplantation's unquestionable potential.

Keywords: Genetic engineering; Genetic-engineered animals; Kidney xenotransplantation; Xenoantigen; Xenotransplantation; Zoonoses.

Fig. 1

Variation of transgene expression in pigs. Immunohistochemistry in A and B with brown stating representing pig cells with human transgene. Kidney immunofluorescence in C with pink staining representing human transgene expression. A Difference in expression of human thrombomodulin in the heart and kidneys from a single pig. Reused and modified with permission from [32]. B Expression level of each of the six transgenes in the same kidney on the 10-GE pig transplanted in a brain-dead human. Reused and modified with permission from [••]. C Difference in expression of different human transgenes in pig TKO-A and TKO-B. Pig A was considered positive for CD46, CD55, and CD59 but with low expression and had high expression of HLA-E and CD47. Pig B was considered to have high expression of CD46, CD55, and CD59 and moderate expression of HLA-E and CD47. PD-L1 was only added to pig A and expressed in a high amount. Reused with permission from [48]