Culture of patient-derived multicellular clusters in suspended hydrogel capsules for pre-clinical personalized drug screening

• DOI: 10.1016/j.bioactmat.2022.03.020
• Publication Date: 2022-03-19T20:20:08Z
• Authors: Haijiang Dong; Zequn Li; Suchen Bian; Guangyuan Song; Wenfeng Song; Mingqi Zhang; Haiyang Xie; Shusen Zheng; Xuxu Yang; Tiefeng Li; Penghong Song
• Keywords: Personalized Medicine

A personalized medication regimen provides precise treatment for an individual and can be guided by pre-clinical drug screening. The economical high-efficiency simulation of the liver tumor microenvironment (TME) in a drug-screening model has high value yet challenging to accomplish. Herein, we propose TME with suspended alginate-gelatin hydrogel capsules encapsulating patient-derived multicellular clusters, culture organoids(PDTOs) capsule offers 3D matrix environment mechanical biological properties similar those vivo. As result, 18 28 clusters were successfully cultured as PDTOs. These PDTOs, along hepatocyte growth factor (HGF) non-cellular components, preserve stromal cells, including cancer-associated fibroblasts (CAFs) vascular endothelial cells (VECs). They also maintain stable expression molecular markers heterogeneity original tumors. Drugs, cabazitaxel, oxaliplatin, sorafenib, tested sensitivity PDTOs these drugs differs between individuals. one PDTO oxaliplatin was validated using magnetic resonance imaging (MRI) biochemical tests after clinical corresponding patient. Therefore, this approach is promising economical, accurate, high-throughput screening treatment.