Abstract
To test the safety and efficacy of drugs via a high does drug heat map, a multi-spheroids array chip was developed by adopting a micropillar and microwell structure. In the chip, patient-derived cells were encapsulated in alginate and grown to maturity for more than 7 days to form cancer multi-spheroids. Multi-spheroids grown in conventional well plates require many cells and are easily damaged as a result of multiple pipetting during maintenance culture or experimental procedures. To address these issues, we applied a micropillar and microwell structure to the multi-spheroids array. Patient-derived cells from patients with Glioblastoma (GBM), the most common and lethal form of central nervous system cancer, were used to validate the array chip performance. After forming multi-spheroids with a diameter greater than 100μm in a 12×36 pillar array chip (25mm × 75mm), we tested 70 drug compounds (6 replicates) using a high-dose to determine safety and efficacy for drug candidates. Comparing the drug response of multi-spheroids derived from normal cells and cancer cells, we found that four compounds (Dacomitinib, Cediranib, LY2835219, BGJ398) did not show toxicity to astrocyte cell and were efficacious to patient-derived GBM cells.
Highlights
The 2D monolayer cell culture model has traditionally been used to evaluate the response of cancer cells to different anti-cancer drug compounds
The micropillar/microwell chip platform was used for short term cell culture to form spheroids. When we applied this to long term multi-spheroids cell culture, we found that the low volume of media (1 μL) in each microwell evaporated quickly and there was a lack of CO2 supply in the tightly packed chips
In order to carry out a longterm cell culture, the culture medium must be changed which poses a risk that the cells may be damaged or lost during this process
Summary
The 2D monolayer cell culture model has traditionally been used to evaluate the response of cancer cells to different anti-cancer drug compounds. Multi-spheroid cancer array chip for high-dose drug heat map analysis.
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