Research article summary (published 12 Mar 2007):

Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke.

Full 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.

Author information

Author/s: Zacharek, Alex (A); Chen, Jieli (J); Cui, Xu (X); Li, Ang (A); Li, Yi (Y); Roberts, Cynthia (C); Feng, Yifan (Y); Gao, Qi (Q); Chopp, Michael (M);

Affiliation: Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan, USA.

Grants: P01 NS23393 (Agency:NINDS NIH HHS) ; R01 NS047682 (Agency:NINDS NIH HHS) ; R01 NS047682-03 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab), published in United States. (Language: eng)

Reference: 2007-Oct; vol 27 (issue 10) : pp 1684-91

Dates: Created 2007/09/20; Completed 2007/10/17; Revised 2009/05/08;

PMID: 17356562, status: MEDLINE (last retrieved date: 5/11/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Angiopoietin-1 - metabolism Animals Astrocytes - metabolism Blood-Brain Barrier - metabolism; pathology Bone Marrow Cells - metabolism Cells, Cultured Coculture Techniques Endothelial Cells - metabolism Gene Expression Regulation Male

Mice Mice, Knockout Neovascularization, Pathologic - genetics; metabolism; pathology Rats Rats, Wistar Receptor, TIE-2 - deficiency; genetics; metabolism Stroke - metabolism; pathology Stromal Cells - metabolism Vascular Endothelial Growth Factor A - metabolism Vascular Endothelial Growth Factor Receptor-2 - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Angiopoietin-1 (0) ; Vascular Endothelial Growth Factor A (0) ; Receptor, TIE-2 (EC 2.7.1.112) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.1.112)

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