TY - JOUR
KW - Astrocytes
KW - Blood-Brain Barrier
KW - Coculture Techniques
KW - Endothelial Cells
KW - Humans
KW - Ischemic Stroke
KW - Lab-On-A-Chip Devices
KW - Microglia
KW - Microvessels
KW - Models, Biological
KW - Neurons
KW - Pericytes
KW - Stem Cell Transplantation
KW - Stem cells
AU - Zhonglin Lyu
AU - Jon Park
AU - Kwang-Min Kim
AU - Hye-Jin Jin
AU - Haodi Wu
AU - Jayakumar Rajadas
AU - Deok-Ho Kim
AU - Gary K. Steinberg
AU - Wonjae Lee
AB - 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.
BT - Nature Biomedical Engineering
DA - 2021-08
DO - 10.1038/s41551-021-00744-7
IS - 8
LA - eng
N2 - 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.
PY - 2021
SP - 847
EP - 863
T2 - Nature Biomedical Engineering
TI - A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke
VL - 5
SN - 2157-846X
ER -