Background: During nephron induction, morphogenetic molecules are reciprocally exchanged between epithelial and mesenchymal stem/progenitor cells within the renal stem/progenitor cell niche. That these molecules remain concentrated, it is assumed that both cell populations stand in close contact to each other. However, recently published data illustrate that epithelial and mesenchymal cells are separated by an astonishingly wide interstitial interface. Methods: To gain deeper morphological insights into the spatial distribution of mesenchymal and epithelial stem/progenitor cells, the embryonic zone of neonatal rabbit kidney was fixed either with glutaraldehyde (GA) or in a combination with cupromeronic blue, ruthenium red or tannic acid. Transmission electron microscopy was then performed on exactly orientated sections. Results: Conventional fixation with GA illustrates that epithelial and mesenchymal stem/progenitor cells are separated by a bright but inconspicuously looking interstitial interface. In contrast, fixation of specimens in GA containing cupromeronic blue, ruthenium red or tannic acid elucidates that part of the interstitial interface exhibits a special extracellular matrix extending like woven strands between mesenchymal and epithelial stem/progenitor cells. In parallel, filigree projections from mesenchymal stem/progenitor cells cross the interstitial interface to penetrate the basal lamina of epithelial cells. Fusion of the plasma membranes cannot be observed. Instead, touching mesenchymal cell projections form a cone at the contact site with tunneling nanotubes. Conclusions: The results demonstrate that the contact between mesenchymal and epithelial stem/progenitor cells does not form accidentally but physiologically and appears to belong to a suspected system involved in the exchange of morphogenetic information.

Caldas HC, Hayashi AP, Abbud-Filho M: Repairing the chronic damaged kidney: the role of regenerative medicine. Transplant Proc 2011;43:3573-3576.
Burst V, Pütsch F, Kubacki T, Völker LA, Bartram MP, Müller RU, Gillis M, Kurschat CE, Grundmann F, Müller-Ehmsen J, Benzing T, Teschner S: Survival and distribution of injected haematopoietic stem cells in acute kidney injury. Nephrol Dial Transplant 2012 (E-pub ahead of print).
Rak-Raszewska A, Wilm B, Edgar D, Kanny S, Woolf AS, Murray P: Development of embryonic stem cells in recombinant kidneys. Organogenesis 2012;8.
Cavaglieri RC, Martini D, Sogayar MC, Noronha IL: Mesenchymal stem cells delivered at the subcapsule of the kidney ameliorate renal disease in the remnant kidney model. Transplant Proc 2012;41:947-951.
Chuasuwan A, Kellum JA: Acute kidney injury and its management. Contrib Nephrol. Basel, Karger, 2011, vol 171, pp 218-225.
Satwani P, Bavishi S, Jin Z, Jacobson JS, Baker C, Duffy D, Lowe L, Morris E, Cairo MS: Risk factors associated with kidney injury and the impact of kidney injury on overall survival in pediatric recipients following allogeneic stem cell transplant. Biol Blood Marrow Transplant 2011;17:1472-1480.
Baddour JA, Sousounis K, Tsonis PA: Organ repair and regeneration: an overview. Birth Defects Res C Embryo Today 2012;96:1-29.
Wise AF, Ricardo SD: Mesenchymal stem cells in kidney inflammation and repair. Nephrology (Carlton) 2012;17:1-19.
Fanni D, Gerosa C, Nemalato S, Mocci C, Pichiri G, Coni P, Congiu T, Piludu M, Piras M, Fraschini M, Zaffanello M, Iacovidou N, Van Eyken P, Monga G, Faa G, Fanos V: Physiological renal regenerating medicine in VLBW preterm infants: could a dream come true? J Matern Fetal Neonatal Med 2012;3:41-48.
Xinaris C, Morigi M, Benedetti V, Imberti B, Fabricio AS, Squarcina E, Beneigni A, Gagliardini E, Remuzzi G: A novel strategy to enhance mesenchymal stem cell migration capacity and promote tissue repair in an injury specific fashion. Cell Transplant 2013;22:423-436.
Little MH, McMahon AP: Mammalian kidney development: principles, progress, and projections. Cold Spring Harb Perspect Biol 2012;4.
Faa G, Gerosa C, Fanni D, Monga G, Zaffanello M, Van Eyken P, Fanos V: Morphogenesis and molecular mechanisms involved in human kidney development. J Cell Physiol 2012;227:1257-1268.
Schumacher K, Strehl R, de Vries U, Groune HJ, Minuth WW: SBA-positive fibers between the CD ampulla, mesenchyme, and renal capsule. J Am Soc Nephrol 2002;13:2446-2453.
Piludu M, Fanos V, Congiu T, Piras M, Gerosa C, Mocci C, Fanni D, Nemolato S, Muntoni S, Iacovidou N, Faa G: The pine-cone body: an intermediate structure between the cap mesenchyme and the renal vesicle in the developing nod mouse kidney revealed by an ultrastructural study. J Matern Fetal Neonatal Med 2012;25:72-75.
Park HC, Yasudu K, Kuo MC, Ni J, Ratliff B, Chander P, Goligorsky MS: Renal capsule as a stem cell niche. Am J Physiol Renal Physiol 2010;298:F1254-F1262.
Minuth WW, Denk L, Miess, Glashauser A: Peculiarities of the extracellular matrix in the interstitium of the renal stem/progenitor cell niche. Histochem Cell Biol 2011;136:321-334.
Hasko JA, Richardson GP: The ultrastructural organization and properties of the mouse tectorial membrane matrix. Hear Res 1988;35:21-38.
Rothenburger M, Völker W, Vischer P, Glasmacher B, Scheid HH, Deiwick M: Ultrastructure of proteoglycans in tissue-engineered cardiovascular structures. Tissue Eng 2002;8:1049-1056.
Minuth WW, Denk L: Illustration of extensive extracellular matrix at the epithelial mesenchymal interface within the renal stem/progenitor cell niche. BMC Clin Pathol 2012;12:16.
Bates CM: Role of fibroblast growth factor receptor signalling in kidney development. Am J Physiol Renal Physiol 2011;301:F245-F251.
Nakamura J, Yanagita M: Bmp modulators in kidney disease. Discov Med 2012;13:57-63.
Rolf HJ, Niebert S, Niebert M, Gaus L, Schliephake H, Wiese KG: Intercellular transport of Oct4 in mammalian cells: a basic principle to expand a stem cell niche? PLoS One 2012;7:e32287.
Domhan S, Ma L, Tai A, Anaya Z, Beheshti A, Zeier M, Hlatky L, Abdollahi A: Intercellular communication by exchange of cytoplasmic material via tunneling nano-tube like structures in primary human renal epithelial cells. PLoS One 2011;6:e21283.
Veranic P, Lokar M, Schütz GJ, Weghuber J, Wiser S, Hägerstrand H, Kralj-Iglic V, Iglic A: Different types of cell-to-cell connections mediated by nanotubular structures. Biophys J 2008;95:4416-4425.
Gurke S, Barroso JF, Gerdes HH: The art of cellular communication: tunnelling nanotubes bridge the divide. Histochem Cell Biol 2008;129:539-550.
Lehtonen E: Epithelio-mesenchymal interface during mouse kidney tubule induction in vivo. J Embryol Exp Morphol 1975;34:695-705.
Osawa T: Regeneration of the epidermis and mucosal epithelium on the basement membranes. Med Electron Microsc 2003;36:193-203.
Yeager M, Harris Al: Gap junction channel structure in the early 21st century: facts and fantasies. Curr Opin Cell Biol 2007;19:521-528.
Medalia O, Geiger B: Frontiers of microscopy-based research into cell-matrix adhesions. Curr Opin Cell Biol 2010;22:659-668.
Wartiovaara J, Nordling S, Lehtonen E, Saxen L: Transfilter induction of kidney tubules: correlation with cytoplasmic penetration into nucleopore filters. J Embryol Exp Morphol 1974;31:667-682.
Lehtonen E, Wartiovaara S, Nordling S, Saxen L: Demonstration of cytoplasmic processes in Millipore filters permitting kidney tubule induction. J Embryol Exp Morphol 1975;33:187-203.
You do not currently have access to this content.