Abstract
An increasing number of investigations is dealing with the repair of acute and chronic renal failure by the application of stem/progenitor cells. However, accurate data concerning the cell biological mechanisms controlling the process of regeneration are scarce. For that reason new implantation techniques, advanced biomaterials and morphogens supporting regeneration of renal parenchyma are under research. Special focus is directed to structural and functional features of the interface between generating tubules and the surrounding interstitial space. The aim of the present experiments was to investigate structural features of the interstitium during generation of tubules. Stem/progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of a polyester fleece to create an artificial interstitium. Perfusion culture was performed for 13 days in chemically defined Iscove’s Modified Dulbecco’s Medium containing aldosterone (1 × 10−7 M) as tubulogenic factor. Recordings of the artificial interstitium in comparison to the developing kidney were performed by morphometric analysis, scanning and transmission electron microscopy. The degree of differentiation was registered by immunohistochemistry. The data reveal that generated tubules are embedded in a complex network of fibers consisting of newly synthesized extracellular matrix proteins. Morphometric analysis further shows that the majority of tubules within the artificial interstitium develops in a surprisingly close distance between 5 and 25 μm to each other. The abundance of synthesized extracellular matrix acts obviously as a spacer keeping generated tubules in distance. For comparison, the same principle of construction is found in the developing parenchyma of the neonatal kidney. Most astonishingly, scanning electron microscopy reveals that the composition of interstitial matrix is not homogeneous but differs along a cortico-medullary axis of proceeding tubule development.
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Anglani, F., et al. The renal stem cell system in kidney repair and regeneration. Front. Biosci. 13:6395–6405, 2008.
Ash, S. R., F. E. Cuppage, M. E. Hoses, and E. E. Selkurt. Culture of isolated renal tubules: a method of assessing viability of normal and damaged cells. Kidney Int. 1:55–60, 1975.
Burns, W. C., P. Kantharidis, and M. C. Thomas. The role of tubular epithelial-mesenchymal transition in progressive kidney disease. Cells Tissues Organs 1–3:222–231, 2007.
Bussolati, B., and G. Camussi. Stem cells and repair of kidney damage. G Ital Nefrol. 2:161–168, 2008.
Chhabra, P., and K. L. Brayman. The use of stem cells in kidney disease. Curr. Opin. Org. Transplant. 1:72–78, 2009.
Eddy, A. A. Progression in chronic kidney disease. Adv. Chronic Kidney Dis. 4:353–365, 2005.
Fleischmajer, R., et al. Immunochemical analysis of human kidney reticulin. Am. J. Pathol. 5:1225–1235, 1992.
Giuliani, S., et al. Ex vivo whole embryonic kidney culture: a novel method for research in development, regeneration and transplantation. J. Urol. 1:365–370, 2008.
Grobstein, C. Trans-filter induction of tubules in mouse metanephrogenic mesenchyme. Exp. Cell Res. 2:424–440, 1956.
Hamilton, A. M., and J. J. Heikkila. Examination of the stress-induced expression of the collagen binding heat shock protein, hsp47, in Xenopus laevis cultured cells and embryos. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 1:133–141, 2006.
Heber, S., L. Denk, K. Hu, and W. W. Minuth. Modulating the development of renal tubules growing in serum-free culture medium at an artificial interstitium. Tissue Eng. 2:281–292, 2007.
Hopkins, C., J. Li, F. Rae, and M. H. Little. Stem cell options for kidney disease. J. Pathol. 2:265–281, 2009.
Iwano, M., et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest. 3:341–350, 2002.
Kaissling, B., and M. Le Hir. The renal cortical interstitium: morphological and functional aspects. Histochem. Cell Biol. 2:247–262, 2008.
Kloth, S., et al. Transitional stages in the development of the rabbit renal collecting duct. Differentiation 1:21–32, 1998.
Manwell, L. A., and J. J. Heikkila. Examination of KNK437- and quercetin-mediated inhibition of heat shock-induced heat shock protein gene expression in Xenopus laevis cultured cells. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 3:521–530, 2007.
Minuth, W. W., A. Blattmann, L. Denk, and H. Castrop. Mineralocorticoid receptor, heat shock proteins and immunophilins participate in the transmission of the tubulogenic signal of aldosterone. J. Epithel. Biol. Pharmacol. 11:24–34, 2008.
Minuth, W. W., L. Denk, K. Hu, H. Castrop, and C. Gomez-Sanchez. The tubulogenic effect of aldosterone is attributed to intact binding and intracellular response of the mineralocorticoid receptor. Cent. Eur. J. Biol. CEJB 2(3):3307–3325, 2007.
Minuth, W. W., L. Sorokin, and K. Schumacher. Generation of renal tubules at the interface of an artificial interstitium. Cell. Physiol. Biochem 4–6:387–394, 2004.
Nigam, S. K., and M. M. Shah. How does the ureteric bud branch? J. Am. Soc. Nephrol. 20:1465–1469, 2009.
Razzaque, M. S., V. T. Le, and T. Taguchi. Heat shock protein 47 and renal fibrogenesis. Contrib. Nephrol. 148:57–69, 2005.
Razzaque, M. S., et al. Synthesis of type III collagen and type IV collagen by tubular epithelial cells in diabetic nephropathy. Pathol. Res. Pract. 11:1099–1104, 1995.
Sariola, H. Nephron induction. Nephrol. Dial. Transplant. 17(9):88–90, 2002.
Saxén, L., and E. Lehtonen. Embryonic kidney in organ culture. Differentiation 1:2–11, 1987.
Schmidt-Ott, K. M., et al. Novel regulators of kidney development from the tips of the ureteric bud. J. Am. Soc. Nephrol. 7:1993–2002, 2005.
Schumacher, K., R. Strehl, and W. W. Minuth. Characterization of micro-fibers at the interface between the renal collecting duct ampulla and the cap condensate. Nephron. Exp. Nephrol. 2:e43–e54, 2003.
Strehl, R., S. Kloth, J. Aigner, P. Steiner, and W. W. Minuth. PCDAmp1, a new antigen at the interface of the embryonic collecting duct epithelium and the nephrogenic mesenchyme. Kidney Int. 6:1469–1477, 1997.
Strehl, R., and W. W. Minuth. Partial identification of the mab (CD)Amp1 antigen at the epithelial-mesenchymal interface in the developing kidney. Histochem. Cell Biol. 5:389–396, 2001.
Strehl, R., V. Trautner, S. Kloth, and W. W. Minuth. Existence of a dense reticular meshwork surrounding the nephron inducer in neonatal rabbit kidney. Cell Tissue Res. 3:539–548, 1999.
Sutterlin, G. G., and G. Laverty. Characterization of a primary cell culture model of the avian renal proximal tubule. Am. J. Physiol. 1 Pt 2:R220–R226, 1998.
Xu, G., and X. Liu. Aldosterone induces collagen synthesis via activation of extracellular signal-regulated kinase 1 and 2 in renal proximal tubules. Nephrology (Carlton) 8:694–701, 2008.
Yokoo, T., A. Fukui, K. Matsumoto, and M. Okabe. Stem cells and kidney organogenesis. Front. Biosci. 13:2814–2832, 2008.
Zeisberg, E. M., S. E. Potenta, H. Sugimoto, M. Zeisberg, and R. Kalluri. Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J. Am. Soc. Nephrol. 12:2282–2287, 2008.
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Associate Editor Michael S. Detamore oversaw the review of this article.
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Miess, C., Glashauser, A., Denk, L. et al. The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney. Ann Biomed Eng 38, 2197–2209 (2010). https://doi.org/10.1007/s10439-010-0006-6
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DOI: https://doi.org/10.1007/s10439-010-0006-6