PT  - JOURNAL ARTICLE
AU  - Disha Sood
AU  - Dana M. Cairns
AU  - Jayanth M. Dabbi
AU  - Charu Ramakrishnan
AU  - Karl Deisseroth
AU  - Lauren D. Black III
AU  - Sabato Santaniello
AU  - David L. Kaplan
TI  - Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix
AID  - 10.1101/691907
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 691907
4099  - http://biorxiv.org/content/early/2019/07/04/691907.short
4100  - http://biorxiv.org/content/early/2019/07/04/691907.full
AB  - 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.