Life happens in (at least) three dimensions. Studying its molecular and cellular basis in flat cells attached to hard plastic, revealing though this is about some aspects of biology, will only take us so far. But scientists have recently added a shiny new tool to their belts: three-dimensional multicellular stem-cell-derived constructs that mimic in vivo tissue, or organoids. For their fascinating potential as tools to probe human biology and disease, we have chosen organoids as Method of the Year 2017.

Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, often manifesting at the advanced stage when cure is no longer possible. The discrepancy between preclinical findings and clinical outcome in HCC is well-recognized. So far, sorafenib is the only targeted therapy approved as first-line therapy for patients with advanced HCC. There is an urgent need for improved preclinical models for the development of HCC-targeted therapies. Patient-derived xenograft (PDX) tumor models have been shown to closely recapitulate human tumor biology and predict patient drug response. However, the use of PDX models is currently limited by high costs and low throughput. In this study, we engineered in vitro conditions conducive for the culture of HCC-PDX organoids derived from a panel of 14 different HCC-PDX lines through the use of a three-dimensional macroporous cellulosic sponge system. To validate the in vitro HCC-PDX models, both in vivo and in vitro HCC-PDX models were subjected to whole exome sequencing and RNA-sequencing. Correlative studies indicate strong concordance in genomic and transcriptomic profiles as well as intra-tumoral heterogeneity between each matched in vitro-in vivo HCC-PDX pairs. Furthermore, we demonstrate the feasibility of using these in vitro HCC-PDX models for drug testing, paving the way for more efficient preclinical studies in HCC drug development.

Copyright © 2018 Elsevier Ltd. All rights reserved.

Three-dimensional tissue culture makes the in vitro observation closer to the original environment of the body tissue. Many studies have found that Patient-derived Organoid (PDO) can provide a more similar growth environment, for organ-like observation and drug testing than two- dimensional culture. 

Our company has our own “stent patent” and "PDO culture patent”. This product contains tissue lysis buffer, three-dimensional culture stent (CelluSponge) and cell culture kits. This PDO kit provides complete PDO culture components ,and it can accelerate the proscess of clinical and research application for drug testing and screening.

Abstract

Hepatocellular carcinoma (HCC) treatments are evaluated by two‐dimensional (2D) in vitro culture systems, despite their limited ability to predict drug efficacy. The three‐dimensional (3D) microporous scaffold provides the possibility of generating more reliable preclinical models to increase the efficacy of cancer treatments. The physical properties of a microporous cellulosic scaffold were evaluated. The cellulosic scaffold was biocompatible and had a highly porous network with appropriate pore size, swelling rate, and stiffness of cancer cell cultures. Cellulosic scaffolds were compared with 2D polystyrene for the culture of HepG2 and Huh7 human HCC cells. Cellulosic scaffolds promoted tumor spheroid formation. Cells cultured on scaffolds were more resistant to chemotherapy drugs and showed upregulation of EpCAM and Oct4. The migration ability of HCC cells cultured on scaffolds was significantly greater than that of cells grown in 2D cultures as evidenced by the downregulation of E‐cadherin. In addition, the proportion of CD44+/CD133+ HCC cancer stem cells (CSCs) was significantly greater in cells cultured on scaffolds than in those grown in 2D cultures. These findings suggest that cellulosic scaffolds effectively mimic the in vivo tumor behavior and may serve as a platform for the study of anticancer therapeutics and liver CSCs.