Fetal rhesus monkey model of obstructive renal dysplasia

Abstract

These results demonstrate the importance of this nonhuman primate model for exploring the pathophysiology of congenital obstructive uropathy and highlight the potential role of podocyte injury in determining long-term renal function associated with this condition.

Remodeling of the Fetal Collecting Duct Epithelium

“…8 In both humans and in our previously described non-human primate model, 10 urinary tract obstruction results in significant CD dilatation, the formation of peritubular collars, fibrosis of the adjacent interstitium, and phenotypic changes to the epithelium. 10,26 In addition, obstruction in both models results in a reduction of ICs from 18% to 8% of CD cells in the term nonhuman primate, and 10.7 to 3.8% in the postnatal human, indicating a change in the cell composition and therefore in the function of these tubular segments.…”

Vesicoureteral Reflux

“…45 Studies have shown that induced obstruction in animal fetuses results in renal parenchymal abnormality, but presence of VUR was not determined. 46,47 The second theory proposes that abnormal ureteric budding and/or dysfunctional interactions between the ureteric bud and metanephric mesenchyme give rise to VUR and other renal abnormalities 48. Mouse embryo studies 38,49,50 demonstrate that abnormal ureteric budding was evident in many of the mice that developed renal tract anomalies. Investigators propose that abnormal budding explains the occurrence of VUR.…”

Fetal Gene Therapy

“…It was not surprising, therefore, when we examined other tissues of the recipients, to find that gene transfer was not limited to cells of the hematopoietic system, but had occurred in essentially all of the organs we examined, including numerous cell types within the liver, lung, and brain [79,81,82,86]. Concomitantly, in utero gene transfer studies performed by other investigators in sheep, rodent, and non-human primate models employing a variety of viral-based gene delivery vectors produced similar results [78][79][80][81][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105], raising the exciting possibility that in utero gene therapy could potentially be used to treat not only hematologic disorders, but also numerous genetic disorders that affect tissues other than the hematopoietic system. For example, in the case of the hemophilias, this method could likely be used with success to delivering genes for the missing coagulation factors to the developing liver at levels that would covert patients with severe hemophilia to a moderate or even mild phenotype [79].…”