4.4 Article

Combination of endothelial progenitor cells and BB-94 significantly alleviates brain damage in a mouse model of diabetic ischemic stroke

Journal

EXPERIMENTAL AND THERAPEUTIC MEDICINE
Volume 22, Issue 1, Pages -

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2021.10221

Keywords

endothelial progenitor cells; BB-94; matrix metalloproteinases; ischemic stroke

Funding

  1. National Natural Science Foundation of China [81860321]

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The study aimed to investigate the effects of endothelial progenitor cells (EPCs) and the matrix metalloproteinase inhibitor BB-94 on diabetic ischemic stroke. In vitro experiments showed that BB-94 promoted cell proliferation and prevented apoptosis, while the combination of EPCs and BB-94 further accelerated proliferation and mitigated oxidative damage. In vivo experiments demonstrated that EPCs and BB-94 alleviated cerebral ischemia/reperfusion injury in a mouse model.
Ischemic stroke is a complication of chronic macrovascular disease in type 2 diabetes. However, the pathogenesis of diabetic ischemic stroke has not yet been fully clarified. The aim of the present study was to investigate the underlying effects of endothelial progenitor cells (EPCs) and the matrix metalloproteinase inhibitor BB-94 on diabetic stroke. In vitro experiments were performed using oxygen-glucose deprivation/reoxygenation (OGD/R) model cells, established using HT22 mouse hippocampal cells. MTT assays and flow cytometry revealed that BB-94 prominently induced the proliferation of the OGD/R model cells and prevented their apoptosis. When EPCs and BB-94 were applied to the OGD/R model cells in combination, proliferation was further accelerated and oxidative damage was attenuated. In vivo experiments were also performed using a middle cerebral artery occlusion (MCAO) mouse model. The results of modified neurological severity scoring and oxidative stress marker analysis demonstrated that EPCs and BB-94 prominently alleviated cerebral ischemia/reperfusion injury in the MCAO model mice. Furthermore, reverse transcription-quantitative PCR and western blot assays revealed that EPCs in combination with BB-94 significantly downregulated the expression of matrix metalloproteinases (MMPs) and upregulated the expression of tissue inhibitor of metalloproteinases 1 in OGD/R cells and MCAO model mice. The results suggest that EPCs were successfully isolated and identified, and the OGD/R cell and MCAO mouse models were successfully established. They also indicate that EPCs alone or in combination with BB-94 may exert protective effects against ischemic stroke via the reduction of MMP expression.

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