Overexpression of VLA-4 in glial-restricted precursors enhances their endothelial docking and induces diapedesis in a mouse stroke model.

Autor: Jablonska A; 1 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA.; 2 Institute for Cell Engineering, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, USA., Shea DJ; 3 Department of Chemical & Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, USA., Cao S; 1 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA.; 2 Institute for Cell Engineering, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, USA., Bulte JW; 1 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA.; 2 Institute for Cell Engineering, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, USA.; 3 Department of Chemical & Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, USA.; 4 Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, USA.; 5 Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, USA., Janowski M; 1 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA.; 2 Institute for Cell Engineering, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, USA.; 6 NeuroRepair Department, Mossakowski Medical Research Centre, Warsaw, Poland., Konstantopoulos K; 3 Department of Chemical & Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, USA., Walczak P; 1 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA.; 2 Institute for Cell Engineering, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, USA.; 7 Department of Radiology, University of Warmia and Mazury, Olsztyn, Poland.
Jazyk: angličtina
Zdroj: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2018 May; Vol. 38 (5), pp. 835-846. Date of Electronic Publication: 2017 Apr 24.
DOI: 10.1177/0271678X17703888
Abstrakt: The loss of oligodendrocytes after stroke is one of the major causes of secondary injury. Glial-restricted progenitors (GRPs) have remylenating potential after intraparenchymal cerebral transplantation. The intraarterial (IA) injection route is an attractive gateway for global brain delivery, but, after IA infusion, naive GRPs fail to bind to the cerebral vasculature. The aim of this study was to test whether overexpression of Very Late Antigen-4 (VLA-4) increases endothelial docking and cerebral homing of GRPs in a stroke model. Mouse GRPs were co-transfected with DNA plasmids encoding VLA-4 subunits (α4, β1). The adhesion capacity and migration were assessed using a microfluidic assay. In vivo imaging of the docking and homing of IA-infused cells was performed using two-photon microscopy in a mouse middle cerebral artery occlusion (MCAO) model. Compared to naïve GRPs, transfection of GRPs with VLA-4 resulted in >60% higher adhesion (p < 0.05) to both purified Vascular Cell Adhesion Molecule-11 (VCAM-11) and TNFα-induced endothelial VCAM-1. VLA-4 + GRPs displayed a higher migration in response to a chemoattractant gradient. Following IA infusion, VLA-4 + GRPs adhered to the vasculature at three-fold greater numbers than naïve GRPs. Multi-photon imaging confirmed that VLA-4 overexpression increases the efficiency of GRP docking and leads to diapedesis after IA transplantation. This strategy may be further exploited to increase the efficacy of cellular therapeutics.
Databáze: MEDLINE
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