Microporous cellulosic scaffold as a spheroid culture system modulates chemotherapeutic responses and stemness in hepatocellular carcinoma

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.

Antioxidant and Antiproliferative Activities of Cyanidin‐3‐O‐Glucoside (C3G) Liposome in Caco‐2 Cells Cultivated in 2D and 3D Cell Culture Models

“…At the same time, the 3D cell culture model was developed as a new in vitro cell culture model. The cells cultured in 3D cell culture model exhibit features that are close to the complex in vivo conditions and have been proven realistic for translating the study findings for in vivo applications (Saglam‐Metiner, Gulce‐Iz, & Biray‐Avci, ; Swaminathan, Hamid, Sun, & Clyne, ; Wu et al., ). In this work, we used hydrogel built the 3D cell culture model, this method is inconvenient and time consuming.…”

The Effect of 2D and 3D Cell Cultures on E-Cadherin Profile and Drug Resistance in Huh7 Cell

“…Several studies have indicated that hepatocellular carcinoma lines in 3D culture show increased treatment resistance compared with those in traditional 2D culture [28][29][30][31][32][33] . To assess the drug resistance of Huh7 cells in 3D culture for a speci c drug when compared with its 2D counterpart, IC 50 was used as the measurement value of the drug's effect on cell activity.…”

Targeting cancer stem cells with polymer nanoparticles for gastrointestinal cancer treatment

“…The CSCs cultured on the 3D cellulose scaffold are spherical, making the cells have a better nutritional status, better simulate the living environment and interaction of CSCs, and enrich CD44+/CD133+ cells. Therefore, the structure of the cellulose scaffold and its physical and biological characteristics promote the growth and efficient enrichment of CSCs [ 35 ]. In general, two main methods are used to isolate and culture CSCs.…”