Endothelial progenitor cells transplantation attenuated blood-brain barrier damage after ischemia in diabetic mice via HIF-1αReportar como inadecuado

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Stem Cell Research and Therapy

, 8:163

First Online: 11 July 2017Received: 08 December 2016Revised: 20 April 2017Accepted: 07 June 2017


BackgroundBlood-brain barrier impairment is a major indicator of endothelial dysfunction in diabetes. Studies showed that endothelial progenitor cell EPC transplantation promoted angiogenesis and improved function recovery after hind limb ischemia in diabetic mice. The effect of EPC transplantation on blood-brain barrier integrity after cerebral ischemia in diabetic animals is unknown. The aim of this study is to explore the effect of EPC transplantation on the integrity of the blood-brain barrier after cerebral ischemia in diabetic mice.

MethodsEPCs were isolated by density gradient centrifugation and characterized by flow cytometry and immunostaining. Diabetes was induced in adult male C57BL-6 mice by a single injection of streptozotocin at 4 weeks before surgery. Diabetic mice underwent 90-minute transient middle cerebral artery occlusion surgery and received 1 × 10 EPCs transplantation immediately after reperfusion. Brain infarct volume, blood-brain barrier permeability, tight junction protein expression, and hypoxia inducible factor-1α HIF-1α mRNA level were examined after treatment.

ResultsWe demonstrated that neurological deficits were attenuated and brain infarct volume was reduced in EPC-transplanted diabetic mice after transient cerebral ischemia compared to the controls p < 0.05. Blood-brain barrier leakage and tight junction protein degradation were reduced in EPC-transplanted mice p <0.05. EPCs upregulated HIF-1α expression while HIF-1α inhibitor PX-478 abolished the beneficial effect of EPCs.

ConclusionsWe conclude that EPCs protected blood-brain barrier integrity after focal ischemia in diabetic mice through upregulation of HIF-1α signaling.

KeywordsBlood-brain barrier Diabetes Endothelial progenitor cell HIF-1α Ischemic stroke AbbreviationsBBBBlood-brain barrier

EPCEndothelial progenitor cell

HIF-1αHypoxia-inducible factor-1α

IgGImmunoglobulin G

MCAOMiddle cerebral artery occlusion

mNSSModified neurological severity score

MSCMesenchymal stem cell

PBSphosphate-buffered saline


TJTight junction

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Autor: Jieli Geng - Liping Wang - Meijie Qu - Yaying Song - Xiaojie Lin - Yajing Chen - Muyassar Mamtilahun - Shengdi Chen - Zhij

Fuente: https://link.springer.com/

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