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Functioning Human Neural Networks Grown in 3-D from Stem Cells

Reporter: Irina Robu, PhD

Researchers at Tuffs University developed three-dimensional human tissue model that mimics structural and functional features of the brain and were able to demonstrate sustained neural activity over several months. The 3D brain tissue models were the result of a collaborative effort between researchers from Tufts University School of Engineering, Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences at Tufts, and the Jackson Laboratory.

These tissue models have the ability to populate a 3D matrix of silk protein and collagen with cells from patients with Parkinson’s disease, Alzheimer’s disease and the ability to

• explore cell interactions,
• disease progression and
• response to treatment.

The 3D brain tissue models overcome a crucial challenge of previous models which is the availability of human source neurons due to the fact that neurological tissues are rarely removed from

• healthy patients, and are usually available
• post-mortem from diseased patients.

The 3D tissue models are populated with human induced pluripotent stem cells (iPSCs) that can be derived from several sources, including patient skin. The iPSCs are generated by turning back the clock on cell development to their embryonic-like precursors. They can then be dialed forward again to any cell type, including neurons. The porous structure of the 3D tissue cultures labeled in the research delivers sufficient oxygenation, access for nutrients and measurement 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.

According to David L. Kaplan, “the silk-collagen scaffolds provide the right environment to produce cells with the genetic signatures and electrical signaling found in native neuronal tissues”. Compared to growing and culturing cells in two dimensions, the three-dimensional matrix yields a knowingly extra complete mix of cells found in neural tissue, with the appropriate morphology and expression of receptors and neurotransmitters. Other researchers have used iPSCs to create brain-like organoids, but can still make it difficult figuring out what individual cells are doing in real time. Likewise, cells in the center of the organoids may not obtain enough oxygen or nutrients to function in a native state.

However, the researchers can see a great advantage of the 3D tissue models with advanced imaging techniques, and the addition of cell types such as microglia and endothelial cells,to create a more complete model of the brain environment and the complex interactions that are involved in

• signaling,
• learning and plasticity, and
• degeneration.

SOURCE

https://www.rdmag.com/news/2018/10/scientists-grow-functioning-human-neural-networks-3d-stem-cells