Recreating the extracellular matrix: novel 3D cell culture platforms in cancer research

Abstract

Cancer initiation and progression heavily rely on microenvironmental cues derived from various components of the niche including the extracellular matrix (ECM). ECM is a complex macromolecular network that governs cell functionality. Although the two‐dimensional (2D) cell culture systems provide useful information at the molecular level and preclinical testing, they could not accurately represent the in vivo matrix microenvironmental architecture. Hence, it is no surprise that researchers in the last decade have focussed their efforts on establishing novel advanced in vitro culture models that mimic tumour and tissue‐specific niches and interactions. These numerous three‐dimensional (3D) culture systems that are now widely available, as well as those still under development, grant researchers with new, improved tools to study cancer progression and to explore innovative therapeutic options. Herein, we report on the emerging methods and cutting‐edge technologies in 3D cell culture platforms and discuss their potential use in unveiling tumour microenvironmental cues, drug screening and personalized treatment.

Physiologic media renders human iPSC-derived macrophages permissive forM. tuberculosisby rewiring organelle function and metabolism

“…Despite the advancing understanding of environmental influences on metabolism, these traditional media continue to serve as the standard for in vitro studies across diverse biological research disciplines 21 . The emergence of physiologic media, along with other initiatives aimed at enhancing the modelling capabilities of cell culture 22 , harbours significant promise for advancing our understanding of fundamental cellular processes 5,[23][24][25] . This is particularly relevant in the context of the establishment of defined and robust culture conditions for iPSC and iPSC-differentiated cell types.…”

Optimization of a Three-Dimensional Culturing Method for Assessing the Impact of Cisplatin on Notch Signaling in Head and Neck Squamous Cell Carcinoma (HNSCC)

“…However, these simple but utterly reductionist cell cultures have a wide range of limitations. They fail to mimic the basic physiological conditions found in tumor tissues, including, among others: (a) the lack of proper cell-cell and cell-matrix interactions, (b) the absence of any mechanical properties prevalent in tumor tissues, (c) inadequate representation of metabolic gradients, (d) the lack of oxygen gradients and hypoxia [41][42][43], (e) acquiring a forced apical-basal polarity not found in tumor cells embedded within cancer tissues, and (f) as a consequence, they fail to mimic the characteristic tumor histology or architecture. As a result, 2D monolayer and monoculture models often exhibit marked hypersensitivity to cytostatic drugs which are preferentially targeting hyperproliferation and induce growth arrest and/or programmed cell death/apoptosis.…”

Extracellular matrix biomechanical roles and adaptation in health and disease

“…Extracellular matrices, as dynamic and adaptive 3D scaffolds, display regulatory roles in tissue morphogenesis and define the biochemical and biomechanical properties of all tissues and organs [3,4]. ECM provides physical cues to cells through its mechanical properties, including stiffness and elasticity.…”