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Little attention received developmental aspects of the human kidney during the late phase of gestation. For healthy newborn babies this subject has no further meaning, since nephrogenesis proceeds unnoticed until birth. Upon delivery, morphogenic activity in the nephrogenic zone is waning and progenitor cell niches aligned beyond the renal capsule disappear by an unknown mechanism. However, a comparable but too early degenerative process takes place in the kidneys of preterm and low birth weight babies. Although born in a period of active nephrogenesis, pathological findings show that they evolve to a high incidence oligonephropathy. Regarding this problematic situation, it is necessary to develop concepts for a therapeutic prolongation of nephrogenesis. However, their realization will be difficult. First, many harming molecules and metabolites, related receptors and disturbed pathways on progenitor target cells have to be identified. Due to the lack of an intact vessel system, a site-specific application of drugs is required. Morphological peculiarities of the nephrogenic zone and positioning of niches must be taken into account. Of current interest are cell biological interactions between the nephrogenic zone and the covering capsule. For example, between gestation weeks 32 and 38, an astonishingly big areal expansion of the capsule and the underlying nephrogenic zone in an order of 30% takes place. Data point out that this little-noticed process also has a special meaning for the control of continuation and cessation of nephrogenesis. Thus, the present contribution likes to inform about this network, and it is simultaneously a call for young scientists to start with investigations in a hardly explored claim.

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.

Development of a nephron is induced by a reciprocal exchange of morphogenetic proteins between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. For sustaining concentration of diffusing proteins high, it is believed that an intimate contact exists between involved cells. However, actual morphological data show that both types of stem/progenitor cell bodies are separated by an interface. To analyze details of this arrangement, neonatal rabbit kidneys were fixed in traditional glutaraldehyde (GA) solution for transmission electron microscopy. For an enhanced contrast fixation of samples was performed in GA solution including either cupromeronic blue, ruthenium red or tannic acid. To record always the same perspective, embedded blocks of parenchyma were cut in orientated vertical and transverse planes to the lumen of lining collecting duct tubules. Screening of samples fixed by GA solution demonstrates a constant separation of stem/progenitor cell bodies by an unobstrusively looking interface. In contrast, improved fixation of specimens in GA solution including cupromeronic blue, ruthenium red or tannic acid unveils between them earlier not visible filigree extracellular matrix. Further projections of mesenchymal cells covered by this matrix cross the interface to contact epithelial cells. The end of a projection does not dangle but is mounted by a special plug connection. At this site the plasma membranes of mesenchymal and epithelial cells are connected via tunneling nanotubes. Regarding this unique arrangement the principal question is to what extent illustrated extracellular matrix and cell-cell connections are involved in the exchange of morphogenetic proteins during induction of a nephron. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano