A comparison between GalT-/-;hCD39;hCD55 and GalT-/-;hCD39;hCD46;hCD55;TBM pig kidney transplanted in non-human primates

Due to shortage of donor kidney, genetically modified kidney xenograft from pigs is considered. To select the optimal gene modification for xenotransplantation, knockout of carbohydrate genes or knockin of protective proteins have been applied. In this study, we utilized GalT- /-;hCD39;hCD55 and GalT-/-;hCD39;hCD46;hCD55;thrombomodulin (TBM) pigs for transplantation in non-human primates. NHPs survived for 4 weeks after kidney transplantation (4 WAT) from GalT-/-;hCD39;hCD55 pig and 6 WAT from GalT- /-;hCD39;hCD46;hCD55;TBM pig. However, mRNA sequencing and immunohistochemistry analysis revealed that 6 WAT kidney showed the severe apoptosis, inflammation, loss of renal function, and renal fibrosis than 4 WAT kidney. These results suggest that additional knockin of anti-complement (hCD26) and anti-coagulation (TBM) is not sufficient to inhibit the renal damage. To select genotype that effectively alleviates immune rejection reponse, we performed comparative transcriptome profiling using mRNA seq data obtained from kidneys of GalT-/-;hCD39;hCD55 and GalT-/-;hCD39;hCD46;hCD55;thrombomodulin (TBM) pigs.