Korean J Transplant.  2023 Nov;37(Suppl 1):S149. 10.4285/ATW2023.F-7349.

Transcriptomic analysis of the coexisting nonhuman primate kidney with a transgenic pig kidney

• Kim Y
• Hanna H
• Sethi G
• Kang G
• Park S
• Hwang J

• KMID: 2551769
• DOI: http://doi.org/10.4285/ATW2023.F-7349

Abstract

Background
Xenotransplantation using a pig’s kidney is a method that serves as a bridge to buy waiting time for allotransplantation to overcome the donor shortage problem. During pig-to-nonhuman primate (NHP) kidney transplantation, it is unclear what happens to NHP kidneys that coexist with the pig kidney.
Methods
NHP kidneys coexisting with pig kidneys for 14 (GTKO/hCD39/hCD55), 67 (GTKO/hCD46), and 75 (GTKO) days were analyzed by mRNA sequencing. Ingenuity pathway analysis was used to analyze the differential-expression data.
Results
The gene expression levels associated with the neutrophil extracellular trap signaling pathway were down-regulated, whereas genes associated with acute phase response signaling were upregulated at day 14 (GTKO/hCD39/hCD55). Also, the genes related to interferon signaling was commonly increased at days 67 (GTKO/hCD46) and 75 (GTKO). A significant decrease in the acute phase responses signaling was observed in the kidney on day 75. Through the gene network in the DEGs following kidney xenotransplantation, The kidney in GTKO/hCD39/hCD55-D14 case shows that systemic inflammation may occur due to innate immune response. The case of GTKO/hCD46-D67 and GTKO-D75 present that they are commonly associated with antiviral response through IRF3 and 9.
Conclusions
A genetically engineered pig kidney could induce the situation of systemic inflammation or antiviral immune responses in a remaining NHP kidney.