Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering

Abstract

Human connective tissues are complex physiological microenvironments favorable for optimal survival, function, growth, proliferation, differentiation, migration, and death of tissue cells. Mimicking native tissue microenvironment using various three-dimensional (3D) tissue culture systems in vitro has been explored for decades, with great advances being achieved recently at material, design and application levels. These achievements are based on improved understandings about the functionalities of various tissue cells, the biocompatibility and biodegradability of scaffolding materials, the biologically functional factors within native tissues, and the pathophysiological conditions of native tissue microenvironments. Here we discuss these continuously evolving physical aspects of tissue microenvironment important for human disease modeling, with a focus on tumors, as well as for tissue repair and regeneration. The combined information about human tissue spaces reflects the necessities of considerations when configuring spatial microenvironments in vitro with native fidelity to culture cells and regenerate tissues that are beyond the formats of 2D and 3D cultures. It is important to associate tissue-specific cells with specific tissues and microenvironments therein for a better understanding of human biology and disease conditions and for the development of novel approaches to treat human diseases.

Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture

“…Hydrogels are commonly classified into two major categories, synthetic and natural, based on the origin and biochemical properties of the source materials used to produce the gel. Although synthetic hydrogels have been used in research fields for decades owing to many advantages, including long service life, high capacity of water absorption, high gel strength, easy availability, low cost, comparably simple fabrication process, adjustable signaling inputs by integration of different extracellular matrix (ECM) proteins or polypeptides, and experimental reproducibility [ 3 ], a growing trend of using hydrogels derived from natural, especially tissue-specific native biomaterials in biomedical and bioengineering applications has become increasingly robust recently [ 5 ].…”

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

“…The preservation of tumor heterogeneity and TME are critical to closely mimic the in vivo situation (5,54). We observed a high degree of heterogeneity between distinct parental tissues -not only the levels of ER-positivity were different, but also the percentages and physical distribution of carcinoma and stromal cells -that were recapitulated in the derived tissue microstructures.…”

Emerging Trends in Information‐Driven Engineering of Complex Biological Systems

“…[184][185][186][187] For example, laminin is abundant in the basement membrane of tissue, which possess a more sheet like structure, whereas interstitial matrices of tissues are chiefly made of fibrillar proteins like collagens I, III, and fibronectin. [193] It can act as a reservoir for latent signaling factors that can be released via degradation and can influence cell processes such as migration and proliferation. [193] It can act as a reservoir for latent signaling factors that can be released via degradation and can influence cell processes such as migration and proliferation.…”

“…[188,189] ECM macromolecules provide structural support and mechanical integrity of the local microenvironment, have attachment sites for cell surface receptors, and regulate growth factors. [193] It can act as a reservoir for latent signaling factors that can be released via degradation and can influence cell processes such as migration and proliferation. [182] Additionally, cells actively remodel their local microenvironment by exerting forces on the matrix, secreting new proteins, or degrading proteins through matrix metalloproteases (MMPs), which in turn leads to changes in the proliferation, migration and adhesion, and creates a complex dynamic reciprocity between cells and the ECM.…”