The rabbit nephrogenic zone in culture: past, present and future as a model to investigate causes of impaired nephrogenesis

Abstract

In preterm infants, intrauterine as well as extrauterine influences are held responsible for causing prematurity of renal parenchyma and impaired nephrogenesis, leading to a high incidence of severe kidney diseases later in life. Although involved noxae and resulting molecular effects are quite different, all of them converge to the nephrogenic zone which is restricted to the outer cortex of a developing kidney. Covered by the organ capsule, it consists of aligned ureteric bud-derived collecting duct (CD) ampullae containing epithelial stem cells, nephrogenic mesenchymal stem cells, renal vesicles and S-shaped bodies. Owing to the complex composition of the nephrogenic zone and the different noxae, it is appropriate to investigate impaired nephrogenesis with an adequate in vitro system. In this case, isolation and culture of the nephrogenic zone from neonatal rabbit kidney is particularly well-suited. As compared to human specimens, it exhibits to a large extend a comparable microarchitecture. However, a decisive advantage is that it can be easily and quickly isolated in original composition with microsurgical techniques. Thus, pieces of the explant are available to a variety of advanced culture experiments. Formation of renal spheroids can be used for drug toxicity testing. Mounting in a tissue carrier makes it possible to register functional differentiation of the CD epithelium. Perfusion culture within an artificial interstitium enables investigation of spatial development of tubules. The present article has been written to inform about past and present results, recognized risks and future challenges.