Abstract

Stem/progenitor cells are promising candidates for a therapy of renal failure. However, sound knowledge about implantation and regeneration is lacking. Therefore, mechanisms leading from stem/progenitor cells into tubules are under research. Renal stem/progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of polyester fleece. It creates an artificial interstitium and replaces coating by extracellular matrix proteins. Tubulogenic development is induced by aldosterone. Electron microscopy illuminates growth of tubules in close vicinity to polyester fibers. Tubules contain a differentiated epithelium. The spatial extension of tubules opens a new strategy for testing morphogenic drugs and biocompatible fleece materials.

Highlights

  • Limited regeneration of renal parenchymaThe capability of parenchyma regeneration is limited in patients with chronic or acute renal failure [1,2,3]

  • Present experiments reveal that culture of renal stem/progenitor cells at the interface of an artificial interstitium appears as an ideal model to investigate stimulating and inhibiting influences of morphogenic drugs and innovative biomaterials on the spatial development of renal tubules

  • Shortage may lead to minor or lacking regeneration, while abundance may provoke cluster formation as a result of malformation. It has to be elaborated, if stem/progenitor cells can be injected in form of accidental spots or if they must be implanted at a special site, in a spatial order and in a certain density

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Summary

Limited regeneration of renal parenchyma

The capability of parenchyma regeneration is limited in patients with chronic or acute renal failure [1,2,3] In view of this clinical background, the question arose as to which molecular processes hamper a diseased kidney to form new parenchyma [4,5,6]. In addition to the source of regenerating cells, the preceding developmental process to form nephron-specific segments is of enormous importance. During this step, the cells have to form spatially organized tubules containing a distinct lumen and a basal lamina [19,20]. Innovative protocols for therapeutic induction and a subsequent guiding of the regeneration process are in the focus of intense research

Sensitivity of renal cells
From cells to parenchyma
The renal stem cell niche
Environment for spatial development
Protecting the developing tissue
Transport of culture medium
Labeling whole mount specimens
Detecting cell biological differentiation
Regarding ultrastructural features
Inducing tubulogenic development
Specifity of aldosterone action
Antagonizing the action of aldosterone
Mineralocorticoid receptor and chaperons
Considerations about Implantation
Finding a solution for rapid micro-vascularization
Using basic sandwich set-ups as a subcapsular implant
Findings
Conclusions
Full Text
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