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bioRxiv · 10.1101/691907

Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain matrix

Kaplan, D. L.·Sood, D.·Cairns, D. M.·Dabbi, J. M.·Ramakrishnan, C.·Deisseroth, K.·Black, L. D.·Santaniello, S.
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Abstract

Brain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and astrocytes. Particularly, fetal brain tissue-derived ECM supported long-term maintenance of differentiated neurons, demonstrated by morphology, gene expression and secretome profiling. Astrocytes were evident within the second month of differentiation, and reactive astrogliosis was inhibited in brain ECM-enriched cultures when compared to unsupplemented cultures. Functional maturation of the differentiated hiNSCs within fetal ECM-enriched cultures was confirmed by calcium signaling and unsupervised cluster analysis. Additionally, the study identified native biochemical cues in decellularized ECM with notable comparisons between fetal and adult brain-derived ECMs. The development of novel brain-specific biomaterials for generating mature in vitro brain models provides an important path forward for interrogation of neuron-glia interactions.

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Kaplan, D. L., Sood, D., Cairns, D. M., Dabbi, J. M., Ramakrishnan, C., Deisseroth, K., Black, L. D., Santaniello, S.. 2019-07-04. Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain matrix. https://doi.org/10.1101/691907

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