3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness.

Judith Pape,Umber Cheema,Mark Emberton

doi:10.3389/fbioe.2021.660502

Judith Pape, Umber Cheema + Show 1 more

Open Access

https://doi.org/10.3389/fbioe.2021.660502

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Abstract

The use of tissue-engineered 3D models of cancer has grown in popularity with recent advances in the field of cancer research. 3D models are inherently more biomimetic compared to 2D cell monolayers cultured on tissue-culture plastic. Nevertheless 3D models still lack the cellular and matrix complexity of native tissues. This review explores different 3D models currently used, outlining their benefits and limitations. Specifically, this review focuses on stiffness and collagen density, compartmentalization, tumor-stroma cell population and extracellular matrix composition. Furthermore, this review explores the methods utilized in different models to directly measure cancer invasion and growth. Of the models evaluated, with PDX and in vivo as a relative “gold standard”, tumoroids were deemed as comparable 3D cancer models with a high degree of biomimicry, in terms of stiffness, collagen density and the ability to compartmentalize the tumor and stroma. Future 3D models for different cancer types are proposed in order to improve the biomimicry of cancer models used for studying disease progression.

Highlights

Bioengineering humanized 3D models of cancer will eventually replace the need for animal models (Kimlin et al, 2013)
This review aims to outline the benefits and limitations of different 3D models currently used whilst exploring how the tumor stroma in particular can be engineered to be biomimetic and tissue specific
A number of these bio-inks have shown cell viability of up to 100% when cells are seeded onto the scaffolds for up to 12 days (Mohanty et al, 2015)

Summary

Introduction

Bioengineering humanized 3D models of cancer will eventually replace the need for animal models (Kimlin et al, 2013). This is an important goal in terms of the 3R (replacement, reduction and refinement) framework to perform more humane animal research (Díaz et al, 2020). The focus has been to utilize different approaches to bioengineer 3D models to better understand tumor growth. These models offer the opportunity to model the cancer mass itself and the surrounding stroma, which is important in promoting and directing cancer invasion (Weigelt et al, 2014). This review aims to outline the benefits and limitations of different 3D models currently used whilst exploring how the tumor stroma in particular can be engineered to be biomimetic and tissue specific

Objectives

Findings

Conclusion