Overview

Well defined, reproducible, biologically relevant, and cost-effective organoid models which mimic the tumour microenvironment are needed for the development of preclinical models for testing novel immunotherapies and developing treatment modalities. 3D hydrogel based cell culture has become a powerful tool for developing these models.

Introduction

GrowDex® hydrogels are plant-derived nanofibrillar cellulose (NFC) hydrogels, which provide an effective and reproducible 3D matrix for various healthy and cancerous cell types. The hydrogels physically resemble the ECM, support cell, spheroid, and organoid growth or formation, whilst allowing cells to produce and remodel the ECM to best suit their needs. The hydrogels are shear thinning, temperature stable, lot-to-lot consistent, and ideal for automated cell-based assays.

Methods

It is known that GrowDex hydrogels can be used to preserve the tumor microenvironment with embedded immune cells for 5-7 days. Specifically, GrowDex was utilised for the patient derived explant culture (PDEC) of fresh patient-derived tumour samples (previously detailed in Haikala, et. al.2019, and Munne et. al. 2021).

Results

It was observed that the tumour phenotype and tumour immune microenvironment could be simultaneously altered by changing the mechanical and biological properties of the matrix. Within a stiff microenvironment, the tumour phenotype mimicked the original tumour and the cytokine environment promoted anti-tumour immunity. Whereas in a soft microenvironment, the phenotype became immunosuppressive, and the tumour cells were more aggressive.

Conclusion

This study, amongst others including GrowDex hydrogels, indicate the need for reproducible, well defined in vitro cell culture models for more accurate disease modelling and drug screening capabilities. Biologically relevant GrowDex hydrogels are a great option, since the properties provide the cells with a 3D microenvironment that best suits the desired phenotype of interest.