Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development.

Abstract:

:Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Sances S,Ho R,Vatine G,West D,Laperle A,Meyer A,Godoy M,Kay PS,Mandefro B,Hatata S,Hinojosa C,Wen N,Sareen D,Hamilton GA,Svendsen CN

doi

10.1016/j.stemcr.2018.02.012

subject

Has Abstract

pub_date

2018-04-10 00:00:00

pages

1222-1236

issue

4

issn

2213-6711

pii

S2213-6711(18)30103-6

journal_volume

10

pub_type

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