Sensor monitoring of organotypic human tumor short term cultures may reveal profiles of metabolism and chemosensitivity

Abstract

Event Abstract Back to Event Sensor monitoring of organotypic human tumor short term cultures may reveal profiles of metabolism and chemosensitivity Martin Brischwein1*, Regina Kleinhans1, Marina Haas1 and Bernhard Wolf1 1 Technische Universitaet Muenchen, Germany Background and aim. There is an urgent clinical demand for improved stratification of cancer patients and allocation into distinct therapeutic regimens. In this proof-of-principle study we analyse the feasibilty of a sensor-based profiling of metabolism and chemosensitivity on an organotypic human breast cancer model preserving the native, heterogeneous character of the tumor tissue. Methods. The approach is based on surgically explanted human breast cancer tissue samples which were subjected to careful slicing preparation (Kleinhans, 2012). These organotypic slices in a size of ≈ 4 µl were subsequently cultured for 3-5 days in an automated assay platform (Wolf, 2013). This platform analyzes the pH and dissolved oxygen values with optochemical sensors in the close vicinity of the tumor slices. Acid extrusion and oxygen consumption rates are determined before, during and after treatments with pharmaceutical compounds. Results . A number of 23 surgical samples was analysed. After the introduction of a careful vibratome slicing protocol the success rate of generating viable short term tumor cultures was generally good. The optimum slice thickness was found to be at 200-250 µm. Both a recording of pre-treatment metabolic profiles (i.e. ratios of extracellular acidification rates and oxygen consumption rates) and assessments of chemoresponses to drugs such as chloracetaldehyde and doxorubicine is feasible. Additionally, a computational reaction-diffusion modelling (Grundl, 2013) allows an estimation of pH and dissolved oxygen values in temporal and spatial resolution for an improved control about physico-chemical conditions of the cellular microenvironment. Conclusions / Discussion. A non-interventional, prospective clinical study should be initiated on the basis of this proof-of-principle research. In such a study, the microphysiometric, sensor-based approach should be complemented by data from histopathological, metabolomic and genomic profiling.