Format

Send to

Choose Destination
Stem Cell Reports. 2018 Apr 10;10(4):1222-1236. doi: 10.1016/j.stemcr.2018.02.012. Epub 2018 Mar 22.

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

Author information

1
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. Electronic address: samuel.sances@cshs.org.
2
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
3
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; iPSC Core, The David Janet Polak Foundation Stem Cell Core Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
4
Emulate Inc., 27 Drydock Avenue, 5th Floor, Boston, MA 02210, USA.
5
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. Electronic address: clive.svendsen@cshs.org.

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.

KEYWORDS:

amyotrophic lateral sclerosis; brain microvascular endothelial cells; disease modeling; iPSC; microfluidic device; microphysiological system; organ-on-chip; spinal cord; spinal motor neurons; vasculature

PMID:
29576540
PMCID:
PMC5998748
DOI:
10.1016/j.stemcr.2018.02.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center