Skip to main content
Log in

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. Anglani, F., et al. The renal stem cell system in kidney repair and regeneration. Front. Biosci. 13:6395–6405, 2008.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. Bussolati, B., and G. Camussi. Stem cells and repair of kidney damage. G Ital Nefrol. 2:161–168, 2008.

    Google Scholar 

  5. Chhabra, P., and K. L. Brayman. The use of stem cells in kidney disease. Curr. Opin. Org. Transplant. 1:72–78, 2009.

    Article  Google Scholar 

  6. Eddy, A. A. Progression in chronic kidney disease. Adv. Chronic Kidney Dis. 4:353–365, 2005.

    Article  Google Scholar 

  7. Fleischmajer, R., et al. Immunochemical analysis of human kidney reticulin. Am. J. Pathol. 5:1225–1235, 1992.

    Google Scholar 

  8. 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.

    Article  Google Scholar 

  9. Grobstein, C. Trans-filter induction of tubules in mouse metanephrogenic mesenchyme. Exp. Cell Res. 2:424–440, 1956.

    Article  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  Google Scholar 

  12. Hopkins, C., J. Li, F. Rae, and M. H. Little. Stem cell options for kidney disease. J. Pathol. 2:265–281, 2009.

    Article  Google Scholar 

  13. Iwano, M., et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest. 3:341–350, 2002.

    Google Scholar 

  14. Kaissling, B., and M. Le Hir. The renal cortical interstitium: morphological and functional aspects. Histochem. Cell Biol. 2:247–262, 2008.

    Article  CAS  Google Scholar 

  15. Kloth, S., et al. Transitional stages in the development of the rabbit renal collecting duct. Differentiation 1:21–32, 1998.

    Article  Google Scholar 

  16. 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.

    Article  CAS  Google Scholar 

  17. 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.

    Article  CAS  Google Scholar 

  18. 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.

    Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

  20. Nigam, S. K., and M. M. Shah. How does the ureteric bud branch? J. Am. Soc. Nephrol. 20:1465–1469, 2009.

    Article  PubMed  Google Scholar 

  21. Razzaque, M. S., V. T. Le, and T. Taguchi. Heat shock protein 47 and renal fibrogenesis. Contrib. Nephrol. 148:57–69, 2005.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Google Scholar 

  23. Sariola, H. Nephron induction. Nephrol. Dial. Transplant. 17(9):88–90, 2002.

    Article  CAS  Google Scholar 

  24. Saxén, L., and E. Lehtonen. Embryonic kidney in organ culture. Differentiation 1:2–11, 1987.

    Article  Google Scholar 

  25. 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.

    Article  CAS  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

  29. 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.

    Article  Google Scholar 

  30. 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.

    Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. Yokoo, T., A. Fukui, K. Matsumoto, and M. Okabe. Stem cells and kidney organogenesis. Front. Biosci. 13:2814–2832, 2008.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W. W. Minuth.

Additional information

Associate Editor Michael S. Detamore oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-010-0006-6

Keywords

Navigation