Abstract

Background: There have been conflicting observations regarding the receptors utilized by human multipotent mesenchymal bone marrow stromal cells (hMSC) to adhere to endothelial cells (EC). To address the discrepancies, we performed experiments with cells prepared with a standardized, low-density protocol preserving a sub-population of small cells that are rapidly self-renewing.

Methods: Sialyl Lewis X (SLeX) and α4 integrin expression were determined by flow cytometry. Fucosyltransferase expression was determined by quantitative realtime RT-PCR. Cell adhesion assays were carried out with a panel of endothelial cells from arteries, veins and the microvasculature in vitro. In Vivo experiments were performed to determine single cell interactions in the chick embryo chorioallantoic membrane (CAM). The CAM is a well-characterized respiratory organ allowing for time-lapse image acquisition of large numbers of cells treated with blocking antibodies against adhesion molecules expressed on hMSC.

Results: hMSC expressed α4 integrin, SLeX and fucosyltransferase 4 and adhered to human EC from arteries, veins and the microvasculature under static conditions in vitro. In vivo, hMSC rolled on and adhered to arterioles in the chick embryo CAM, whereas control melanoma cells embolized. Inhibition of α4 integrin and/or SLeX with blocking antibodies reduced rolling and adhesion in arterioles and increased embolism of hMSC.

Conclusions: The results demonstrated that rapidly self-renewing hMSC were retained in the CAM because they rolled on and adhered to respiratory arteriolar EC in an α4 integrin- and SLeX-dependent manner. It is therefore important to select cells based on their cell adhesion receptor profile as well as size depending on the intended target of the cell and the injection route.

Department(s)

Biological Sciences

Comments

This work was supported in part by grants from the National Center for Research Resources (P20RR016456), the National Institute of General Medical Sciences (P20GM103424), Louisiana Cancer Research Consortium and the NIH-RCMI grant #5G12RR026260 from the National Institute on Minority Health and Health Disparities (HEM) and P40 RR 17447 from the National Institutes of Health (DJP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords and Phrases

Animals; Arteries; Cell Communication; Cell Line, Tumor; Chick Embryo; Endothelial Cells; Endothelium, Vascular; Flow Cytometry; Humans; Integrin alpha4; Mesenchymal Stromal Cells; Mice; Oligosaccharides

International Standard Serial Number (ISSN)

1932-6203

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2014 McFerrin et al., All rights reserved.

PubMed ID

25144321

Included in

Biology Commons

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