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Treatment with Outgrowth Endothelial Cells Protects Cerebral Barrier against Ischaemic Injury

Kadir, Rais Reskiawan A.; Alwjwaj, Mansour; Bayraktutan, Ulvi

Authors

Rais Reskiawan A. Kadir

Mansour Alwjwaj



Abstract

Background and aims: We have previously reported that outgrowth endothelial cells (OECs) restore cerebral endothelial cell integrity through effective homing to the injury site. This study further investigates whether treatment with OECs can restore blood-brain barrier (BBB) function in both in vitro and in vivo settings of ischaemia-reperfusion injury.
Methods: An in vitro model of human BBB was established by co-culture of astrocytes, pericytes, and human brain microvascular endothelial cells (HBMECs) before exposure to oxygen-glucose deprivation alone, or followed by reperfusion (OGD±R) in the absence or presence of exogenous OECs. Using a rodent model of middle cerebral artery occlusion (MCAO), we further assessed the therapeutic potential of OECs in vivo.
Results: Owing to their prominent anti-oxidant, proliferative, and migratory properties, alongside their inherent capacity to incorporate into brain vasculature, treatments with OECs attenuated the extent of OGD±R injury on BBB integrity and function, as ascertained by increases in transendothelial electrical resistance and decreases in paracellular flux across the barrier. Similarly, intravenous delivery of OECs also led to better barrier protection in MCAO rats as evidenced by significant decreases in ipsilateral brain oedema volumes on day 3 after treatment. Mechanistic studies subsequently showed that treatment with OECs substantially reduced oxidative stress and apoptosis in HBMECs subjected to ischaemic damages.
Conclusion: This experimental study has shown that OEC-based cell therapy restores BBB integrity in an effective manner by integrating into resident cerebral microvascular network, suppressing oxidative stress and cellular apoptosis.

Citation

Kadir, R. R. A., Alwjwaj, M., & Bayraktutan, U. (in press). Treatment with Outgrowth Endothelial Cells Protects Cerebral Barrier against Ischaemic Injury. Cytotherapy,

Journal Article Type Article
Acceptance Date Nov 8, 2021
Deposit Date Nov 25, 2021
Journal Cytotherapy
Print ISSN 1465-3249
Publisher Elsevier
Peer Reviewed Peer Reviewed
Public URL https://nottingham-repository.worktribe.com/output/6788436