Immunohistochemical markers of stem/progenitor cells in the developing human kidney

Sanna, Alice; Fanos, Vassilios; Gerosa, Clara; Vinci, Laura; Puddu, Melania; Loddo, Cristina; Faa, Gavino

doi:10.1016/j.acthis.2015.02.014

Cited by 9 publications

(7 citation statements)

References 11 publications

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“…During the process of nephron induction the tip of each CD ampulla including epithelial stem cells moves towards the inner layer of mesenchymal cells. Hence, only the tip of a single CD ampulla with contained epithelial cells and some of the nearest GDNF + /Six2 + /CITED1 + mesenchymal cells are regarded as an individual renal niche [8,22].…”

Section: Definition Of Niche Sitesmentioning

confidence: 99%

“…Although born in a phase of active nephrogenesis, a high percentage of them evolves oligonephropathy and prematurity of renal parenchyma causing severe restrictions for health later in life [6,7]. Various intra-and extrauterine influences seem to be responsible, but independent from chemical nature all noxious parameters converge finally to the nephrogenic zone and the here contained stem cell niches [8,9].…”

Section: Introductionmentioning

confidence: 99%

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2017

Drug Res (Stuttg)

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Section: Definition Of Niche Sitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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2017

Drug Res (Stuttg)

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“…The subpopulation of mesenchymal cells closest to the epithelium of the CD ampulla represents GDNF + Six2 + cells belonging to the cap mesenchyme (CM). 19 , 20 When nephron induction takes place, some of these cells react by performing a mesenchymal-to-epithelial transition (MET) to develop into epithelial cells of the nephron.…”

Section: Orientation Of Mesenchymal and Epithelial Cells Within The Nmentioning

confidence: 99%

Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction

Minuth

Denk

2016

BioResearch Open Access

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Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of specimens by glutaraldehyde (GA) solution including cupromeronic blue, ruthenium red, or tannic acid for electron microscopy depicts that the interface is not void but filled in extended areas by textured extracellular matrix. Surprisingly, projections of mesenchymal cells cross the interface to contact epithelial cells. At those sites the plasma membranes of a mesenchymal and an epithelial cell are connected via tunneling nanotubes. Regarding detected morphological features in combination with involved morphogens, their transport cannot longer be explained solely by diffusion. Instead, it has to be sorted according to biophysical properties of morphogens and to detected environment. Thus, the new working hypothesis is that morphogens with good solubility such as glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factors (FGFs) are transported by diffusion. Morphogens with minor solubility such as bone morphogenetic proteins (BMPs) are secreted and stored for delivery on demand in illustrated extracellular matrix. In contrast, morphogens with poor solubility such as Wnts are transported in mesenchymal cell projections along the plasma membrane or via illustrated tunneling nanotubes. However, the presence of an intercellular route between mesenchymal and epithelial stem/progenitor cells by tunneling nanotubes also makes it possible that all morphogens are transported this way.

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“…The absence of the blue strip in a preterm newborn might indicate the early cessation of nephrogenesis and that no potential nephrogenesis could go on in that kidney. Recently, our group demonstrated that the cells of the blue strip show a peculiar phenotype characterized by immunoreactivity for Mdm2 and Wingless-type MMTV integration site family, member 1 (Wnt1) [ 25 ]. A study on a baboon model of preterm birth, perinatal exposure to ibuprofen lead to a significantly reduced nephrogenic zone, evidenced at histology by the reduction of the blue strip width, associated with a early cessation of glomerulogenesis [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Each niche has an actor: multiple stem cell niches in the preterm kidney

et al. 2015

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The preterm kidney cannot be simply considered as a kidney small in size: as compared to the adult kidney, the developing organ of the preterm infant is characterized by marked differences regarding the architecture and cell components. At macroscopy, fine linear demarcations indenting the renal surface characterize the fetal and preterm kidney. At microscopy, multiple major architectural changes differentiate the developing kidney from the adult one: a large capsule with a high cellularity; the branching ureteric bud, extending from the hilum towards the renal capsule; striking morphological differences among superficial (just born) and deep (more mature) glomeruli; persistence of remnants of the metanephric mesenchyme in the hylum; incomplete differentiation of developing proximal and distal tubules. At cellular level, kidneys of preterm infants are characterized by huge amounts of stem/precursor cells showing different degrees of differentiation, admixed with mature cell types. The most striking difference between the preterm and adult kidney is represented by the abundance of stem/progenitor cells in the former. Multiple stem cell niches may be identified in the preterm kidney, including the capsule, the sub-capsular nephrogenic zone, the cap mesenchyme embracing the ureteric bud tips, the cortical and medullary interstitium, and the hilar zone in proximity of the ureteric origin. The sub-capsular area represents the major stem cell niche in the prenatal kidney. It has been defined “blue strip”, due to the scarcity of cytoplasm of the undifferentiated stem/progenitors, which appear as small cells arranged in a solid pattern. All these data taken together, the morphological approach to the analysis of the preterm kidney appears completely different from that typically utilized in kidney biopsies from adult subjects. Such a different structure should be taken into account when evaluating renal function in a preterm infant in clinical practice. Moreover, a better knowledge of molecular biology of the blue strip stem/progenitor cells could be at the basis of a new “endogenous” regenerative medicine, finalized to maintain and protect the nephrogenic potential of preterm infants till the 36th week of post-conceptional age, allowing them to escape oligonephronia and chronic kidney disease later in life.

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Immunohistochemical markers of stem/progenitor cells in the developing human kidney

Cited by 9 publications

References 11 publications

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Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction

Each niche has an actor: multiple stem cell niches in the preterm kidney

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