A Neurovascular-unit-on-a-chip for the Evaluation of the Restorative Potential of Stem Cell Therapies for Ischaemic Stroke

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2021 Aug 13

PMID 34385693

Citations 51

Authors

Zhonglin Lyu

Jon Park

Kwang-Min Kim

Hye-Jin Jin

Haodi Wu

Jayakumar Rajadas

Deok-Ho Kim

Gary K Steinberg

Wonjae Lee

Affiliations

Soon will be listed here.

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.

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