Roles of Diffusion Dynamics in Stem Cell Signaling and Three-Dimensional Tissue Development [Research Article in PubMed]

Brief Summary: Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This article describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described in the context of the major molecular signaling pathways in stem cells that both mediate and are influenced by gas and nutrient concentrations, including how diffusion phenomena can affect stem cell state, cell differentiation, and metabolic states of the cell. The application of these diffusion models and pathways is of vital importance for future studies of developmental processes, disease modeling, and tissue regeneration.

The software code and user interface for running these basic sets of diffusion models in MATLAB can be found on GitHub at https://github.com/IONRATE/ORGANOIDS

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References:

McMurtrey RJ. Roles of Diffusion Dynamics and Molecular Concentration Gradients in Cellular Differentiation and Three-Dimensional Tissue Development. Stem Cells and Development. 2017; 26(18):1293-1303. doi: 10.1089/scd.2017.0066 PMID: 28707964 arXiv:1707.08543

McMurtrey RJ. Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids. Tissue Engineering Part C. doi: 10.1089/ten.TEC.2015.0375 PMID: 26650970 arXiv:1512.06475

McMurtrey RJ. Patterned and Functionalized Nanofiber Scaffolds in 3-Dimensional Hydrogel Constructs Enhance Neurite Outgrowth and Directional Control. J. Neural Eng. 11 (2014) 066009 doi:10.1088/1741-2560/11/6/066009 PMID: 25358624 arXiv:1501.01338

McMurtrey RJ. Novel Advancements in Three-Dimensional Neural Tissue Engineering and Regenerative Medicine. Neural Regeneration Research. 2015 Mar; 10(3):352-354. doi: 10.4103/1673-5374.153674 PMID: 25878573 arXiv:1504.00698

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