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Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix. Scientific reports Sood, D. n., Cairns, D. M., Dabbi, J. M., Ramakrishnan, C. n., Deisseroth, K. n., Black, L. D., Santaniello, S. n., Kaplan, D. L. 2019; 9 (1): 17874

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 spectral/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.

View details for DOI 10.1038/s41598-019-54248-1

View details for PubMedID 31784595