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Abstract: In regenerative medicine much attention is given to stem/progenitor cells for a future therapy of acute and chronic renal failure. However, up to date sound cell biological knowledge about nephron renewal in kidney is lacking. For that reason molecular mechanisms are under intense investigation leading from stem/progenitor cells to regenerated tubules. In this coherence new biomaterials and drug delivery systems have to be elaborated showing an intense stimulation on the renewal of parenchyma. To analyze tubule regeneration a powerful culture system is of fundamental importance. An advanced technique stimulates renal stem/progenitor cells to develop numerous tubules between layers of a polyester fleece. Use of chemically defined Iscove''s Modified Dulbecco''s Medium (IMDM) containing aldosterone (1×10−7 M) results in spatial development of renal tubules within 13days of perfusion culture. Immunohistochemistry exhibits that numerous features of a polarized epithelium are expressed in generated tubules. Transmission electron microscopy (TEM) illuminates that generated tubules contain a polarized epithelium with a tight junctional complex and an intact basal lamina at the basal aspect. Development of tubules depends on applied aldosterone concentration and cannot be mimicked by precursors of its synthesis pathway or by other steroid hormones. Antagonists such as spironolactone or canrenoate prevent the development of tubules. This result illuminates that the tubulogenic development is mediated via the mineralocorticoid receptor (MR). Application of geldanamycin, radicicol, quercetin or KNK 437 in combination with aldosterone blocks development of tubules by disturbing the contact between MR and heat shock proteins 90 and 70. In conclusion, for the first time generation of renal tubules can be simulated under controlled in-vitro conditions. Using this model the effect of numerous innovative biomaterials and drug delivery system can be critically analyzed. [Copyright &y& Elsevier]

Abstract: The cell biological mechanism controlling the regeneration of renal tubules in renal failure after application of stem/progenitor cells is subject of actual research. Unsolved issues are the integration of stem/progenitor cells in a diseased organ environment, the differentiation into epithelial tissue and the formation of tubules in a spatial environment. Following this therapeutic strategy new biomaterials have to be found promoting spatial development of tubules. To obtain new information about the growth of tubules renal stem/progenitor cells from neonatal rabbit kidney were isolated and mounted in a tissue carrier between a selection of commercially available polyester fleeces. This procedure replaces coating by extracellular matrix proteins and creates an artificial interstitium supporting development of tubules. Perfusion culture was performed with chemically defined IMDM containing aldosterone as tubulogenic factor. Polyester fleeces were investigated by scanning electron microscopy. The spatial development of tubules was registered on whole-mount specimens and on cryosections labeled with SBA and antibodies indicating tubule differentiation. It is found that some polyester fleeces promote the spatial development of tubules between the fibers, whereat each of them produces its individual growth pattern. [Copyright &y& Elsevier]