Journal of Tissue Science and Engineering

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.

This paper shows the technical feasibility of using a modified double lumen catheter for the delivery of fluids at the skin-catheter interface in an in vivo rabbit model. The modified catheter permits the extrusion of suspensions at the site of contact between the skin and the modified catheter (exit site). The modification consisted in the addition of a second lumen, exterior to the original one of the catheter and of shorter length, ending in an extrusion port placed subdermally. An external fluid pump was attached to the catheter and the whole system was tested in vitro in human skin, in a cadaver model and in an in vivo rabbit model. Experiments were performed by delivering solutions of methylene blue in a controlled manner to the subcutaneous area to analyze the skin response to the process. Results indicate that this technique of pumping the material is effective in producing observable epithelial changes in the short term. The modification of the catheter addresses catheter exit site lack of integration of skin and works as a model that can be implemented in a number of percutaneous devices for long-term implantation.