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

Area of Science:

• Biomaterials Science
• Oncology
• Cell Biology

Background:

• Current 2D in vitro models for hepatocellular carcinoma (HCC) treatments have limited predictive power for drug efficacy.
• Three-dimensional (3D) culture systems are needed to create more reliable preclinical models for cancer therapy.
• Microporous scaffolds offer a promising platform for advanced 3D cell culture.

Purpose of the Study:

• To evaluate the physical properties of a novel microporous cellulosic scaffold for HCC cell culture.
• To compare the performance of cellulosic scaffolds with traditional 2D polystyrene cultures for HCC cells.
• To assess the potential of cellulosic scaffolds as a preclinical model for liver cancer research.

Main Methods:

• Characterization of physical properties (biocompatibility, porosity, pore size, swelling, stiffness) of cellulosic scaffolds.
• Culture of HepG2 and Huh7 human HCC cell lines on both cellulosic scaffolds and 2D polystyrene.
• Assessment of tumor spheroid formation, drug resistance, cell migration, and cancer stem cell populations (EpCAM, Oct4, E-cadherin, CD44+/CD133+).

Main Results:

• Cellulosic scaffolds demonstrated biocompatibility and suitable physical properties for cell culture.
• HCC cells cultured on scaffolds formed tumor spheroids and exhibited increased resistance to chemotherapy.
• Scaffold-cultured cells showed enhanced migration, altered E-cadherin expression, and increased proportions of EpCAM, Oct4, and CD44+/CD133+ cancer stem cells.

Conclusions:

• Cellulosic scaffolds effectively mimic in vivo tumor behavior compared to 2D cultures.
• These 3D scaffolds represent a valuable platform for studying liver cancer stem cells and evaluating anticancer therapeutics.
• The findings support the use of cellulosic scaffolds for developing more predictive preclinical models for HCC.