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

• Published in: Nature biomedical engineering Vol. 5; no. 8; pp. 847 - 863
• Main Authors: Lyu, Zhonglin, Park, Jon, Kim, Kwang-Min, Jin, Hye-Jin, Wu, Haodi, Rajadas, Jayakumar, Kim, Deok-Ho, Steinberg, Gary K., Lee, Wonjae
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2021; Nature Publishing Group
• Subjects: 13/100; 13/107; 13/62; 14/1; 14/19; 14/63; 38/77; 631/378/1689/534; 631/61/2035; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - chemistry; Blood-Brain Barrier - metabolism; Cell therapy; Coculture Techniques; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Gene expression; Humans; Ischemia; Ischemic Stroke - therapy; Lab-On-A-Chip Devices; Microfluidics; Microglia; Microglia - cytology; Microglia - metabolism; Microvasculature; Microvessels - cytology; Models, Biological; Neurons; Neurons - cytology; Neurons - metabolism; Pericytes; Pericytes - cytology; Pericytes - metabolism; Recovery; Regeneration; Stem Cell Transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Stroke; Structure-function relationships
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-021-00744-7

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. A microphysiological model of ischaemic stroke consisting of a functional neurovascular unit on a microfluidic chip allows for the systematic characterization of the neurorestorative outcomes of candidate stem cell therapies.