Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks
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Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks Jakub Sumbal 1
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Zuzana Budkova 2
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Gunnhildur Ásta Traustadóttir 2
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Zuzana Koledova 1
Received: 24 July 2020 / Accepted: 4 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 3D cell culture methods have been an integral part of and an essential tool for mammary gland and breast cancer research for half a century. In fact, mammary gland researchers, who discovered and deciphered the instructive role of extracellular matrix (ECM) in mammary epithelial cell functional differentiation and morphogenesis, were the pioneers of the 3D cell culture techniques, including organoid cultures. The last decade has brought a tremendous increase in the 3D cell culture techniques, including modifications and innovations of the existing techniques, novel biomaterials and matrices, new technological approaches, and increase in 3D culture complexity, accompanied by several redefinitions of the terms “3D cell culture” and “organoid”. In this review, we provide an overview of the 3D cell culture and organoid techniques used in mammary gland biology and breast cancer research. We discuss their advantages, shortcomings and current challenges, highlight the recent progress in reconstructing the complex mammary gland microenvironment in vitro and ex vivo, and identify the missing 3D cell cultures, urgently needed to aid our understanding of mammary gland development, function, physiology, and disease, including breast cancer. Keywords 3D cell culture . Breast . Co-culture . Extracellular matrix . Imaging . Microenvironment . Organoid . Screening . Stromal cells
Introduction Our bodies and organs, including mammary gland, are composed of billions of cells, which are organized in a highly defined manner in three-dimensional (3D) space to perform specific functions. The 3D organization and composition of extracellular matrix (ECM), and the identity and 3D architecture of neighboring cells, form a tissue microenvironment, which is fundamental to cell behavior and differentiation. Thus, tissue microenvironment controls tissue growth, development, homeostasis, and function, and is implicated in disease [1, 2]. Therefore, to faithfully model cell behavior and function in vitro and ex vivo, 3D cell culture techniques are * Gunnhildur Ásta Traustadóttir [email protected] * Zuzana Koledova [email protected] 1
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland
required because they allow replication of crucial cell-cell and cell-ECM interactions of tissues in vivo [3]. By contrast, twodimensional cell cultures on rigid plastic or glass surface do not provide physiologically relevant environmental context, resulting in changes in cell function [4, 5]. The 3D cell culture methods have become staples in the method toolbox of developm
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