Title : Advanced 3D tissue models: Pioneering tools for investigating health and disease
Abstract:
In vitro tissue models are laboratory-grown biological systems that use isolated cells, tissues, or organs to simulate the structure and function of living organisms. Traditional models are two-dimensional (2D) cell cultures, in which cells are grown as a monolayer on flat surfaces. While cost-effective, they often fail to capture complex cell-to-cell and cell-matrix interactions. These models have therefore evolved into more sophisticated three-dimensional (3D) systems that more accurately replicate the native human microenvironment. These models present a major challenge for modern tissue engineering, which now serves not only to replace and regenerate damaged tissues in the body but also to research the physiological development of various issues, as well as the pathogenesis and potential treatment of various diseases. Relatively simple 3D tissue models are spheroids, cellular aggregates formed by primary cells or cell lines in suspension, used for basic drug toxicity and metabolic studies – for example, for glioblastoma research in our laboratory. More complex are organoids, i.e., stem cell-derived, self-organizing 3D structures that mimic the architecture and function of miniature organs (e.g., brain, heart, kidney, liver, or gut organoids). Advanced models include organ-on-a-chip microphysiological systems that combine 3D microtissues with microfluidic channels to simulate physiological conditions such as blood flow, nutrient exchange, and mechanical forces, as well as 3D bioprinted models created by layer-by-layer patterning of living cells and "bioinks" (often hydrogels) to build complex tissue architectures with high spatial precision. Despite all this effort, even 3D tissue models are often simplified, lacking, e.g., vascular complexity. Therefore, in our laboratory, specific attention has been paid to the development of pre-vascularization in the models, usually through the self-organization of vascular endothelial cells and mesenchymal stem cells into tubular capillary-like structures in hydrogel matrices. In this way, we are developing models of physiological tissues, such as skin, the blood vessel wall with vasa vasorum, bone tissue, and the osteochondral interface, as well as various pathologies, such as hypertrophic scar, clubfoot, and Dupuytren's contracture. Our models aim to reduce or eliminate the use of laboratory animals in modern biomedical research, not only for ethical reasons, but also because some diseases lack relevant animal models or because these models do not accurately reflect conditions in the human body. Our models can be applied not only to disease modeling but also to drug discovery, toxicology, and precision medicine, which uses patient-specific cells to create tailored models for evaluating how an individual might respond to specific therapies.
Supported by the Czech Acad. Sci. (Praemium Academiae grant No. AP2202), P JAC Project “ExRegMed” No. CZ.02.01.01/00/22_008/0004562 of the MEYS, CR, co-funded by the European Union, and the Czech Health Research Council, Ministry of Health of the Czech Republic (grant No. NU22-06-00016).
