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

By Disha Sood, Dana M Cairns, Jayanth M Dabbi, Charu Ramakrishnan, Karl Deisseroth, Lauren D. Black, Sabato Santaniello, David L. Kaplan

Posted 04 Jul 2019
bioRxiv DOI: 10.1101/691907 (published DOI: 10.1038/s41598-019-54248-1)

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 differntiation, 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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