Polar application of test substances in organotypic environment and under continuous medium flow: A new tissue-based test concept for a broad range of applications in pharmacotoxicology

We have established a new test concept for in vitro pharmacological trials. Our model employs tissue explants to test compounds for toxicity which ari ses with the metabolic interactions among different cell types. Microsurgic al preparation of tissue explants avoids the destruction of the organ-speci fic tissue architecture. Explants were mounted in tissue carriers to improv e nutrition and handling of the sample. To allow for the omission of serum supplementation of the culture medium, explants were cultured under continu ous medium flow. Test substances are applied considering the polar architec ture of most tissues in vivo, for example, covering the apical aspect of ep ithelia, In principal, all tissues obtained from any species, including man , can be used in this system. A trial application was performed with vitreo us body substitutes, substances used in ophthalmology. One compound had pas sed cell culture tests, but caused massive blood vessel deterioration in vi vo. Using our test system based on the developing renal vessel system, we c ould confirm, within 24 hours, severe vessel damage which resembles the inj ury suffered by the rabbit retina. We demonstrate that an improved tissue c ulture assay is a suitable tool for the detection of toxicity that remained unidentified in cell culture tests. (C) 2000 Elsevier Science Ltd. All rig hts reserved.