Editors' ChoiceTissue Engineering

Culture Shock! Brain-Like Tissue Grown in Vitro Has Potential

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Science Translational Medicine  10 Sep 2014:
Vol. 6, Issue 253, pp. 253ec156
DOI: 10.1126/scitranslmed.3010403

The mind is a beautiful thing, but its complexity makes it extremely difficult to study. Analysis of brain interconnectivity is complicated by the overlapping distribution of functionally distinct neuron populations as well as the technical and ethical challenges of studying real-time neuronal behavior in animal models and humans. Previous studies attempting to grow brain tissue in the lab used neurons suspended in extracellular matrix (ECM)–derived gels, but these gels failed to support functional neuronal connections, possibly because of inadequate mechanical properties and rapid degradation in culture. To overcome these limitations, Tang-Schomer et al. put mind over matter to carefully design biomaterials based on silk scaffolds and collagen gel. These materials showed similar elasticity to mouse and rat brain tissue and slower degradation as compared with that of other ECM gels. Importantly, the self-binding nature of silk allowed the adhesive-free assembly of interlocking pieces, which may facilitate connections of neurons in discrete compartments.

After just 7 days, primary rat cortical neurons organized around the pores of the scaffold and extended long axons into the collagen gel, creating mini-networks reminiscent of the compartmentalized gray and white matter of the brain. Compared with two-dimensional culture or to collagen gel alone, the composite silk-collagen system supported extended viability, the growth of longer axons, and increased expression of genes associated with neuronal adhesion, regenerative growth, and synaptogenesis. Recordings of local field potential showed electrophysiologically relevant behavior in response to treatment with a neurotoxin. Excitingly, the viable brain-like tissue allowed analysis of the effects of a mechanical injury, creating a model of traumatic brain injury (TBI) in a way that has never been possible before. When a weight was dropped onto the tissue, the neurons showed a spike in electrical activity and a rapid release of the neurotransmitter glutamate, similar to what has been observed in animal models of TBI.

Although preliminary, this study represents proof of concept that brain-like tissue grown in vitro can be used to examine physiologically relevant responses to drugs and mechanical injury. Future generations of the biomaterials may include important extracellular matrix components, soluble factors, electrical stimulation, and more highly differentiated cell types in separate compartments. The model must then be extended to human neurons differentiated from induced pluripotent stem cells in order to fully realize its translational potential. Unfortunately, this bioengineered brain is unlikely to help us think, but it can allow detailed studies of the complex behavior of neurons.

M. D. Tang-Schomer et al., Bioengineered functional brain-like cortical tissue. Proc. Nat. Acad. Sci. U.S.A. 10.1073/pnas.1324214111 (2014). [Abstract]

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