Immunofluorescence and Electron Microscopy in Genetically Engineered Pig-to-Human Kidney Xenotransplantation: A Case...

Genetically engineered (GE) porcine kidney xenografts have been used recently in pig-to-human brain-dead decedent xenotransplantation. However, immunofluorescence (IF) and electron microscopy (EM) findings of xenografts have not been fully described. Here we report novel IF and EM features of GE pigs with 10 genetic modifications (10GE) xenografts with clinical correlation in 3 cases of pig-to-human brain-dead decedent xenotransplantation, performed at our institution. Preimplant biopsies unexpectedly demonstrated clinically silent mesangial immune complex deposits in all 3 xenografts, indicating porcine donor-related process. In addition, EM showed intact podocyte foot processes in the absence of endothelial cell injury, and thin glomerular basement membrane relative to adult human glomeruli in the absence of hematuria in donor pigs, likely reflecting normal porcine anatomy. In a third decedent with nephrotic-range proteinuria, foot process effacement did not correlate with the severity of proteinuria. We believe that these findings in 10GE porcine kidney xenografts may serve as a reference for normal xenograft morphology, contribute to establish xenograft rejection criteria, and support genuine need for phase I clinical trials to fully understand the long-term clinical implications of these findings.