Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip

Abstract

Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low. Several methodologies have been developed to address this issue, although no study has compared their efficacy in a controlled fashion. We investigated the effect of two variables in TECPs, specifically, the tissue size and culture vessel on tissue survival using micro-dissected tumor tissue (MDT) and tissue slices which were cultured in microfluidic chips and plastic well plates. Tumor models were produced from ovarian and prostate cancer cell line xenografts and were matched in terms of the specimen, total volume of tissue, and respective volume of medium in each culture system. We examined morphology, viability, and hypoxia in the various tumor models. Our observations suggest that the viability and proliferative capacity of MDTs were not affected during the time course of the experiments. In contrast, tissue slices had reduced proliferation and showed increased cell death and hypoxia under both culture conditions. Tissue slices cultured in microfluidic devices had a lower degree of hypoxia compared to those in 96-well plates. Globally, our results show that tissue slices have lower survival rates compared to MDTs due to inherent diffusion limitations, and that microfluidic devices may decrease hypoxia in tumor models.

Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer

“…In the future, the latter issue can be overcome by advances in live-imaging microscopy, a technique that allows a single tissue slice to be analyzed at multiple time points. Moreover, an adaptation to the cancer-on-chip approach could eventually reduce the amount of tumor material required for the analysis of tumor sensitivity, as well as create a more controllable environment to mimic in vivo pharmacokinetic conditions [ 22 , 23 ].…”

Harnessing the Utility of Ex Vivo Patient Prostate Tissue Slice Cultures

“…They used 3 PDX-TS and found that rocking on a cell strainer (very similar to titanium grids rotating) in serum‐free aDMEM/F12 K medium with R1881 was optimal to preserve proliferation and prevent apoptosis. Proof of concept studies in PDX-TS have developed a method to examine many tissues at once in 96-well format by a method they call micro-dissected tissue (MDT) ( 14 , 15 ). MDT are 500 µm in diameter, compared to normal TS which are 3-5 mm, thus MDT permits more precise tissue acquisition and potentially many more experimental endpoints.…”

“…Dorrigiv et al. optimized this by using cell line xenografts as the tissue source ( 15 ). They also developed a method to create an FFPE microarray from the MDT (MDTMA) ( 14 ).…”

“…DNA damage response of benign radical prostatectomy-derived TS was monitored following ionizing radiation (IR) ( 6 ). They found that IR did not elicit Tyr ( 15 ) and p53 responses in TS and they suggest that absence of these DNA damage response pathways may contribute to carcinogenesis ( 6 ).…”

Radiotherapy on-chip: microfluidics for translational radiation oncology

“…135 Furthermore, ex vivo tumor samples maintain naturally-occurring tumor heterogeneity, as they contain both stroma and tumor cells, thereby retaining the complex interplay between these two cell types. 140–142…”