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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1760    most recent 01408.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Liu, Z. Articles by Bache, R. J. Search for Related Content PubMed PubMed Citation Articles by Liu, Z. Articles by Bache, R. J.

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

¹Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio; and ²Stem Cell Institute, ³Division of Hematology, Oncology, and Transplantation, Department of Medicine, ⁴Division of Cardiology, Minneapolis Veterans Affairs Medical Center, and ⁵Division of Cardiovascular Diseases, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota

Submitted 22 December 2006 ; accepted in final form 30 May 2007

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 N^G-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.

progenitor cells