A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke

Zhonglin Lyu, Jon Park, Kwang Min Kim, Hye Jin Jin, Haodi Wu, Jayakumar Rajadas, Deok Ho Kim, Gary K. Steinberg, Wonjae Lee

Research output: Contribution to journalArticlepeer-review

Abstract

The therapeutic efficacy of stem cells transplanted into an ischaemic brain depends primarily on the responses of the neurovascular unit. Here, we report the development and applicability of a functional neurovascular unit on a microfluidic chip as a microphysiological model of ischaemic stroke that recapitulates the function of the blood–brain barrier as well as interactions between therapeutic stem cells and host cells (human brain microvascular endothelial cells, pericytes, astrocytes, microglia and neurons). We used the model to track the infiltration of a number of candidate stem cells and to characterize the expression levels of genes associated with post-stroke pathologies. We observed that each type of stem cell showed unique neurorestorative effects, primarily by supporting endogenous recovery rather than through direct cell replacement, and that the recovery of synaptic activities is correlated with the recovery of the structural and functional integrity of the neurovascular unit rather than with the regeneration of neurons.

Original languageEnglish (US)
Pages (from-to)847-863
Number of pages17
JournalNature biomedical engineering
Volume5
Issue number8
DOIs
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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