scholarly journals Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening

Author(s):  
Lesley Mathews Griner ◽  
Kalyani Gampa ◽  
Toan Do ◽  
Huyen Nguyen ◽  
David Farley ◽  
...  
2015 ◽  
Vol 3 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Brendan M. Leung ◽  
Sasha Cai Lesher-Perez ◽  
Toshiki Matsuoka ◽  
Christopher Moraes ◽  
Shuichi Takayama

Three-dimensional spheroid cultures have become increasingly popular as drug screening platforms, especially with the advent of different high throughput spheroid forming technologies.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 581-581
Author(s):  
Ricardo J. Antonia ◽  
Kan Toriguchi ◽  
Eveliina Karelehto ◽  
Dania Annuar ◽  
Luika Timmerman ◽  
...  

581 Background: Despite standard treatment with gemcitabine and cisplatin, median survival for unresectable Intrahepatic Cholangiocarcinoma (ICC) is < 1 year. Clearly, novel therapeutic strategies are urgently needed. The paucity of targetable mutations in ICC and the as yet unproven benefit of genetically targeted drugs led us to ask whether a reliable clinical benefit may be revealed by patient-specific therapeutic testing in novel models of ICC. Here we describe our ability to establish patient-derived three-dimensional organoid cultures (PDO) that enable individualized identification of active single agents or drug combinations in surrogate models of ICC. Methods: To model patient-specific drug responses, we used the freshly resected ICCs from small samples of single patient tumors to generate PDXs and PDOs, small spheroidal clusters of tumor cells grown in vitro. We have employed a high-throughput drug screening platform using AI-enhanced robotics (Yamaha Motor Corporation) to identify and distribute single, uniformly sized PDOs into 384-well ultra-low adherent plates. This is coupled with a TECAN D300e drug dispenser that rapidly delivers nanoliter volumes of a 34-drug panel, thereby facilitating rapid, reliable drug response analyses. Results: Our data show that PDOs retain characteristic genomic and histological features of the patients’ tumors. Drug responses were specific to each patient tumor, but PDOs from all patients responded to a greater or lesser degree to mTOR inhibition, suggesting that this pathway is important in ICC. The responses of PDO to the mTOR inhibitor Sapanisertib (INK128), was recapitulated in the same patient’s PDX. Further, INK128 was synergistic with gemcitabine in patient 970 PDOs as well as in vivo in PDX also from patient 970. Conclusions: As it is believed that PDX can predict patient responses to drugs, our results suggest that PDO may also predict patient drug responses. The establishment of PDO may allow economical patient-specific, high throughput drug screens that could ultimately inform clinical practice. [Table: see text]


2019 ◽  
Author(s):  
Sang-Cheol Lee ◽  
Young Saing Kim ◽  
In Gyu Hwang ◽  
Su Jin Lee ◽  
Se Hoon Park

2019 ◽  
Author(s):  
Sang-Cheol Lee ◽  
Young Saing Kim ◽  
In Gyu Hwang ◽  
Su Jin Lee ◽  
Se Hoon Park

Lab on a Chip ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 1755-1763 ◽  
Author(s):  
Bin Chen ◽  
Yue Wu ◽  
Zheng Ao ◽  
Hongwei Cai ◽  
Asael Nunez ◽  
...  

Three-dimensional (3D) culture of multicellular spheroids, offering a desirable biomimetic microenvironment, is appropriate for recapitulating tissue cellular adhesive complexity and revealing a more realistic drug response.


Sign in / Sign up

Export Citation Format

Share Document