Journal
BIOFABRICATION
Volume 12, Issue 3, Pages -Publisher
IOP Publishing Ltd
DOI: 10.1088/1758-5090/ab9491
Keywords
tumor heterogeneity; inkjet printing; single cell; tumor organoid; bladder tumor
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [NRF-2018R1A2A3075391, NRF-2016M1A5A1027599]
- Gyeongbuk Science and Technology Promotion Center of Korea [SF317001A]
- National Research Foundation of Korea [21A20131212415] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Quantification of intratumoral heterogeneity is essential for designing effective therapeutic strategies in the age of personalized medicine. In this study, we used a piezoelectric inkjet printer to enable analysis of intratumoral heterogeneity in a bladder cancer for the first time. Patient-derived tumor organoids were dissociated into single cell suspension and used as a bioink. The individual cells were precisely allocated into a microwell plate by drop-on-demand inkjet printing without any additive or treatment, followed by culturing into organoids for further analysis. The sizes and morphologies of the organoids were observed, so as the expression of proliferation and apoptotic markers. The tumor organoids also showed heterogeneous responses against chemotherapeutic agent. Further, we quantified mRNA expression levels of representative luminal and basal genes in both type of tumor organoids. These results verify the heterogeneous expression of various genes among individual organoids. This study demonstrates that the fully automated inkjet printing technique can be used as an effective tool to sort cells for evaluating intratumoral heterogeneity.
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