Abstract
The prevalence of end stage renal disease (ESRD) is dramatically increasing. It is estimated that the number of people in the United States undergoing treatment for chronic kidney disease will rise from 500,000 to two million by the year 2030. In infants and children, ESRD is commonly caused by developmental abnormalities including obstruction of the fetal urinary tract. Characterization of developing glomerular precursors including renal vesicles, C- and S-shaped bodies, and podocytes is necessary in order to determine effective ways to recapitulate ontogeny with the goal of repair. New strategies to repair damaged organs using decellularized biological scaffolds are being developed, with the hope of using cell therapy for tissue regeneration within a natural framework. Decellularized scaffolds must serve as a support for cellular interactions and not result in an immune response. This study characterizes fetal kidney development in a clinically relevant rhesus monkey model and assesses whether MHC Class I or Class II proteins remain in a decellularized kidney scaffold. This was addressed by staining fetal kidneys across gestation with hematoxylin and eosin (H&E), v and performing immunohistochemistry (IHC) and enzyme-linked immunosorbant assay (ELISA) on fresh kidneys and kidneys decellularized in 1% sodium dodecyl sulfate (SDS). Results show that renal development in the rhesus monkey mimics that in the human. Glomerular precursors are abundant in the cortex during the first and second trimesters, and by the third trimester, nearly all precursors have differentiated to mature glomeruli. Near term kidneys from the fetal rhesus monkey model of obstructive renal dysplasia show cystic glomeruli with cystic dilatation of Bowman’s space, and abnormal glomerular tuft development when compared with unobstructed kidneys. The podocyte marker, WT-1, is strongly expressed in the condensed mesenchyme and nephrogenic zone at the cortical border during the first and second trimesters. By the third trimester, WT-1 expression is confined to mature glomeruli. IHC and ELISA revealed that HLA-E and HLA-DR were removed from the scaffolds during decellularization, while modest amounts of HLA-DQ remained in juvenile decellularized kidney scaffolds. The results from this study add to the growing base of research concerning the use of decellularized scaffolds and will contribute to the ability to repair or replace damaged kidneys in vivo.