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A team of researchers led by Tufts University has developed three-dimensional (3D) human tissue culture models for the central nervous system that mimic the structural and functional features of the brain and demonstrate sustained neuronal activity for several months. With the ability to populate a 3D matrix of silk protein and collagen with cells from patients with Alzheimer's disease, Parkinson's disease and other conditions, tissue models can explore cellular interactions , the progression of the disease and the response to treatment. The development and characterization of the models are described today in ACS Biomaterials Science & Engineering, a journal of the American Chemical Society.
The new models of 3D brain tissue overcome a major challenge of previous models, namely the availability of source neurons. This is because neurological tissues are rarely collected from healthy patients and are usually only available post-mortem in sick patients. 3D tissue models are rather populated with human-induced pluripotent stem cells (iPSCs) that can come from many sources, including the patient's skin. IPSCs are generated by reducing the embryonic precursor to cell development. They can then be compounded again to any cell type, including neurons.
The 3D brain tissue models resulted from a collaborative effort between engineering and the medical sciences. They included researchers from the Tufts University School of Engineering, the Tufts University School of Medicine, the Sackler School of Biomedical Sciences, and the University of Ottawa. Tufts and Jackson's lab.
"We have found the conditions for differentiating iPSCs into different subtypes of neurons, as well as astrocytes supporting growing neural networks," said David L. Kaplan, Ph.D. Stern family engineering, chairman of the chair. from the Department of Biomedical Engineering at the Tufts 'School of Engineering and faculty member of the Tufts' Sackler School of Graduate Biomedical Sciences program. "Silk-collagen scaffolds provide the appropriate environment to produce cells with the genetic signatures and electrical signaling found in native neuronal tissues."
Compared with the growth and culture of two-dimensional cells, the three-dimensional matrix provides a much more complete mixture of cells present in neural tissue, with the appropriate morphology and expression of receptors and neurotransmitters, according to the paper .
Others have used iPSCs to create organoids similar to those of the brain, which are small dense spherical structures useful for understanding brain development and function, but can make it difficult to understand what individual cells do. in real time. In addition, the cells at the center of the organoids may not receive enough oxygen or nutrients to function in the native state. The porous structure of the 3D tissue cultures described in this study provides important oxygenation, access to nutrients and a measure of cellular properties. A clear window in the center of each 3D matrix allows researchers to visualize the growth, organization, and behavior of individual cells.
"The growth of neural networks is sustained and very consistent in 3D tissue models, whether we use cells of healthy individuals or cells of patients with Alzheimer's disease or Parkinson's disease," said William Cantley, Ph.D., graduated from Cell in 2018, Molecular Biology and Development Program at the Sackler School of Graduate Sciences in Biomedical Sciences at Tufts and first author of the study, completed as part of his doctorate. thesis. "This gives us a reliable platform for studying different diseases and the ability to observe what happens to cells in the long run."
The researchers plan to leverage more 3D tissue models with advanced imaging techniques and the addition of other cell types, such as microglia and endothelial cells, to create a model more complete the brain environment and complex interactions involved in signaling, learning and plasticity, and degeneration.
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