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

Samuel Sances, Ritchie Ho, Gad Vatine, Dylan West, Alex Laperle, Amanda Meyer, Marlesa Godoy, Paul S. Kay, Berhan Mandefro, Seigo Hatata, Chris Hinojosa, Norman Wen, Dhruv Sareen, Geraldine A. Hamilton, Clive N. Svendsen

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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. Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development.

Original languageEnglish
Pages (from-to)1222-1236
Number of pages15
JournalStem Cell Reports
Volume10
Issue number4
DOIs
StatePublished - 10 Apr 2018
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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