Will W. Minuth, Lucia Denk and Anne Glashauser
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 within the diseased kidney is lacking. Of special interest are steroid hormones occurring in the interstitial fluid. It is unknown, if they have promoting or hampering effects on the development of stem/progenitor cells. To investigate the influence of steroid hormones on regenerating tubules a realistic culture system is of great importance. An advanced technique creates an artificial interstitium promoting renal stem/progenitor cells to develop tubules between layers of polyester fleece. During perfusion culture with chemically defined Iscove’s Modified Dulbecco’s Medium (IMDM) individual steroid hormones can be administered. After a culture period of 13 days the effect on tubule development is analyzed by histochemical methods. Present experiments reveal that substances such as cholesterol and 17-α-hydroxyprogesterone do not exhibit a visible effect on renal stem/progenitor cells. However, atypical aggregation of few SBA-labeled cells in form of islets is found after treatment with progesterone, pregnenolone, 11-deoxycorticosterone and dihydrotestosterone. Numerous SBA-labeled cells within extended clusters are observed after application of testosterone, 17-β-estradiol, corticosterone and dexamethasone. In contrast, application of aldosterone exclusively leads to the formation of numerous intact tubules. In consequence, it is shown that distinct steroid hormones induce a shift in development from intact tubules to atypical cell islets and clusters. Such harmful effects have to be considered, when stem/progenitor cells are exposed after implantation to the interstitial fluid within diseased renal parenchyma.
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