Cited by 298Angiogenesis and VEGF in CancerBarrier Structure and Function StudiesMesenchymal stem cell research

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Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

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Zacharek, Alex, Chen, Jieli, Li, Ang, Cui, Xu, Li, Yi, Roberts, Cynthia, Feng, Yifan, Gao, Qi, Chopp, Michael·2007·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/sj.jcbfm.9600475PMC PMC2796470

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Abstract

Bone marrow stromal cells (MSCs) increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis after stroke. Angiopoietin-1 (Ang1) and its receptor Tie2 mediate vascular integrity and angiogenesis as does VEGF and its receptors. In this study, we tested whether MSC treatment of stroke increases Ang1/Tie2 expression, and whether Ang1/Tie2 with VEGF / vascular endothelial growth factor receptor 2 (VEGFR2) (Flk1), in combination, induced by MSCs enhances angiogenesis and vascular integrity. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without MSCs. Marrow stromal cell treatment significantly decreased blood—brain barrier (BBB) leakage and increased Ang1, Tie2, and occludin (a tight junction protein) expression in the ischemic border compared with MCAo control. To further test the mechanisms of MSC-induced angiogenesis and vascular stabilization, cocultures of MSCs with mouse brain endothelial cells (MBECs) or astrocytes were performed. Supernatant derived from MSCs cocultured with MBECs significantly increased MBEC expression of Ang1/Tie2 and Flk1 compared with MBEC alone. Marrow stromal cells cocultured with astrocytes also significantly increased astrocyte VEGF and Ang1/Tie2 expression compared with astrocyte culture alone. Conditioned media from MSCs alone, and media from cocultures of MSCs with astrocytes or MBECs, all significantly increased capillary tube-like formation of MBEC compared with control Dulbecco's modified Eagle's medium media. Inhibition of Flk1 and/or Ang1 significantly decreased MSC-induced MBEC tube formation. Knockdown of Tie2 expression in MBECs significantly inhibited MSC-induced tube formation. Our data indicate MSC treatment of stroke promotes angiogenesis and vascular stabilization, which is at least partially mediated by VEGF/Flk1 and Ang1/Tie2.

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Self-citation
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Intravenous injection of neural progenitor cells facilitates angiogenesis after cerebral ischemia
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MesenchymAl stromal cells for Traumatic bRain Injury (MATRIx): a study protocol for a multicenter, double-blind, randomised, placebo-controlled phase II trial
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Expression of circulating vascular endothelial growth factor-antagonizing cytokines and vascular stabilizing factors prior to and following bypass surgery in patients with moyamoya disease
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Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
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Therapeutic properties of mesenchymal stem cells for autism spectrum disorders
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Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization
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Self-citation
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Effect of 8-O-acetyl Shanzhiside Methylester Increases Angiogenesis and Improves Functional Recovery after Stroke
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Self-citation
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Link Between Cancer Stem Cells and Adult Mesenchymal Stromal Cells: Implications for Cancer Therapy
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Enhanced repair processes and iron uptake by ischemic preconditioning in the brain during the recovery phase after ischemic stroke
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Mesenchymal stem cells in cancer therapy; the art of harnessing a foe to a friend.
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The effect of human umbilical cord-derived mesenchymal stem cell conditioned medium on the peripheral nerve regeneration of injured rats
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Support of Hepatic Regeneration by Trophic Factors from Liver-Derived Mesenchymal Stromal/Stem Cells
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Authors: Zacharek, A., Chen, J., Li, A., Cui, X., Li, Y., Roberts, C., Feng, Y., Gao, Q., & Chopp, M.
Affiliations: Henry Ford Health (US)
Corresponding author: Chopp, Michael
ORCID: Chen, Jieli
Li, Ang
Cui, Xu
Roberts, Cynthia
Feng, Yifan
Gao, Qi
Chopp, Michael
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2007-10
Volume: 27
Issue: 10
Pages: 1684-1691
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1038/sj.jcbfm.9600475
PMC: PMC2796470
OpenAlex: W1974547403
Cited by: 297
References: 36
Citations by year: 2026: 7 · 2025: 11 · 2024: 15 · 2023: 10 · 2022: 8 · 2021: 23 · 2020: 13 · 2019: 13 · 2018: 13 · 2017: 27 · 2016: 20 · 2015: 18 · 2014: 21 · 2013: 16 · 2012: 22
FWCI: 5.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS047682, P01NS23393, P01NS023393)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: mesenchymal stem cells, stroke, angiogenesis, angiopoietin-1, Tie2, vascular endothelial growth factor, Flk-1, vascular stabilization, blood-brain barrier disruption, occludin, tight junctions, brain endothelial cells, astrocytes, middle cerebral artery occlusion, capillary tube formation, cell therapy
MeSH terms: Animals, Astrocytes, Blood-Brain Barrier, Bone Marrow Cells, Cells, Cultured, Gene Expression Regulation, Male, Neovascularization, Pathologic, Stromal Cells, Rats, Wistar, Mice, Knockout, Coculture Techniques, Stroke, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Angiopoietin-1, Endothelial Cells, Receptor, TIE-2, Mice, Rats

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Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

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