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Cited by 48Barrier Structure and Function StudiesAngiogenesis and VEGF in CancerExtracellular vesicles in disease

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

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Geng, Jieli, Wang, Liping, Qu, Meijie, Song, Yaying, Lin, Xiaojie, Chen, Yajing, Mamtilahun, Muyassar, Chen, Shengdi, Zhang, Zhijun, Wang, Yongting, Yang, Guo-Yuan·2017·Stem Cell Research & Therapy
DOI 10.1186/s13287-017-0605-3PMC PMC5505148
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Abstract

Blood-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. EPCs 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 6 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. We 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. We conclude that EPCs protected blood-brain barrier integrity after focal ischemia in diabetic mice through upregulation of HIF-1α signaling.

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  • Transplantation of mesenchymal cells or endothelial progenitors capable of differentiating in vivo into vascular cells such as pericytes has shown promising results as vascular regeneration therapy and repair BBB damage treatment after stroke.

    “In addition, transplantation of mesenchymal cells or endothelial progenitors that are capable of differentiating in vivo into vascular cells such as pericytes has shown promising results as vascular regeneration therapy (353) and repair BBB damage treatment after stroke (198).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [198]

    The Results section ('EPC therapy attenuated the BBB impairment after tMCAO in diabetic mice') reports that EPC transplantation reduced BBB leakage after ischemic stroke in diabetic mice, supporting the BBB-repair part of the claim. The paper does not show that transplanted cells differentiated into pericytes; its Discussion says the injected EPCs were not tracked and suggests an indirect protective effect. It also cautions that MSC therapy might increase BBB damage in diabetic rats. (LLM, conf=0.86)

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Metadata

Authors
Geng, J., Wang, L., Qu, M., Song, Y., Lin, X., Chen, Y., Mamtilahun, M., Chen, S., Zhang, Z., Wang, Y., & Yang, G.-Y.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
  • Wang, Yongting
  • Yang, Guo-Yuan
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2017-07-11
Volume
8
Issue
1
Pages
163-163
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-017-0605-3
PMC
PMC5505148
OpenAlex
W2734893372
Cited by
48
References
2
Citations by year
2026: 1 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 8 · 2019: 10 · 2018: 8 · 2017: 1
FWCI
3.68
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (81522015, 81371305)
  • the Science and Technology Commission of Shanghai Municipality (13ZR1422600)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
endothelial progenitor cells, cell transplantation, blood-brain barrier, cerebral ischemia, diabetes mellitus, HIF-1α, tight junction proteins, blood-brain barrier permeability, ischemic stroke, brain infarct volume, hypoxia, PX-478, streptozotocin-induced diabetes
MeSH terms
Animals, Blood-Brain Barrier, Brain Ischemia, Diabetes Mellitus, Experimental, Male, Signal Transduction, Up-Regulation, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Endothelial Progenitor Cells

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