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Journal of Cellular Biochemistry

Mesenchymal stem cell modification of endothelial matrix regulates their vascular differentiation

Authors

  • Thomas P. Lozito,

    1. Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892
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  • Juan M. Taboas,

    1. Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892
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  • Catherine K. Kuo,

    1. Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892
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  • Rocky S. Tuan

    Corresponding author
    1. Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892
    • Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1140, MSC 8022, Bethesda, MD 20892-8022.
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

  • This manuscript is Part 2 of 2. Part 1 is described in the manuscript entitled “Human Mesenchymal Stem Cells Express Vascular Cell Phenotypes Upon Interaction With Endothelial Cell Matrix,” which has also been submitted to the Journal of Cellular Biochemistry under reference number JCB-09-0120.

Abstract

Mesenchymal stem cells (MSCs) respond to a variety of differentiation signal provided by their local environments. A large portion of these signals originate from the extracellular matrix (ECM). At the same time, MSCs secrete various matrix-altering agents, including proteases, that alter ECM-encoded differentiation signals. Here we investigated the interactions between MSC and ECM produced by endothelial cells (EC-matrix), focusing not only on the differentiation signals provided by EC-matrix, but also on MSC-alteration of these signals and the resultant affects on MSC differentiation. MSCs were cultured on EC-matrix modified in one of three distinct ways. First, MSCs cultured on native EC-matrix underwent endothelial cell (EC) differentiation early during the culture period and smooth muscle cell (SMC) differentiation at later time points. Second, MSCs cultured on crosslinked EC-matrix, which is resistant to MSC modification, differentiated towards an EC lineage only. Third, MSCs cultured on EC-matrix pre-modified by MSCs underwent SMC-differentiation only. These MSC-induced matrix alterations were found to deplete the factors responsible for EC-differentiation, yet activate the SMC-differentiation factors. In conclusion, our results demonstrate that the EC-matrix contains factors that support MSC differentiation into both ECs and SMCs, and that these factors are modified by MSC-secreted agents. By analyzing the framework by which EC-matrix regulates differentiation in MSCs, we have uncovered evidence of a feedback system in which MSCs are able to alter the very matrix signals acting upon them. J. Cell. Biochem. 107: 706–713, 2009. Published 2009 Wiley-Liss, Inc.

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