Endothelial nitric oxide synthase is dynamically expressed during bone marrow stem cell differentiation into endothelial cells

Zhenguo Liu, Yuehua Jiang, Hong Hao, Kalpna Gupta, Jian Xu, Ling Chu, Edward O McFalls, Jay Zweier, Catherine Verfaillie, Robert J Bache

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29 Scopus citations


This study was designed to investigate the developmental expression of endothelial nitric oxide synthase (eNOS) during stem cell differentiation into endothelial cells and to examine the functional status of the newly differentiated endothelial cells. Mouse adult multipotent progenitor cells (MAPCs) were used as the source of stem cells and were induced to differentiate into endothelial cells with vascular endothelial growth factor (VEGF) in serum-free medium. Expression of eNOS in the cells during differentiation was evaluated with real-time PCR, nitric oxide synthase (NOS) activity, and Western blot analysis. It was found that eNOS, but no other NOS, was present in undifferentiated MAPCs. eNOS expression disappeared in the cells immediately after induction of differentiation. However, eNOS expression reoccurred at day 7 during differentiation. Increasing eNOS mRNA, protein content, and activity were observed in the cells at days 14 and 21 during differentiation. The differentiated endothelial cells formed dense capillary networks on growth factor-reduced Matrigel. VEGF-stimulated phosphorylation of extracellular signal-regulated kinase (ERK)-1 and ERK-2 occurred in these cells, which was inhibited by NOS inhibitor NG-nitro-L-arginine methyl ester. In conclusion, these data demonstrate that eNOS is present in MAPCs and is dynamically expressed during the differentiation of MAPCs into endothelial cells in vitro.

Original languageEnglish (US)
Pages (from-to)H1760-H1765
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3
StatePublished - Sep 2007

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Copyright 2008 Elsevier B.V., All rights reserved.


  • Progenitor cells

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