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J. Biol. Chem., Vol. 282, Issue 46, 33507-33514, November 16, 2007

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A New Role of Thrombopoietin Enhancing ex Vivo Expansion of Endothelial Precursor Cells Derived from AC133-positive Cells^*

Toshie Kanayasu-Toyoda, Akiko Ishii-Watabe, Takayoshi Suzuki, Tadashi Oshizawa, and Teruhide Yamaguchi¹

From the Divisions of Biological Chemistry and Biologicals, and Cellular and Gene Therapy Products, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagayaku, Tokyo 158-8501, Japan

We previously reported that CD31^bright cells, which were sorted from cultured AC133⁺ cells of adult peripheral blood cells, differentiated more efficiently into endothelial cells than CD31⁺ cells or CD31^- cells, suggesting that CD31^bright cells may be endothelial precursor cells. In this study, we found that CD31^bright cells have a strong ability to release cytokines. The mixture of vascular endothelial growth factor (VEGF), thrombopoietin (TPO), and stem cell factor stimulated ex vivo expansion of the total cell number from cultured AC133⁺ cells of adult peripheral blood cells and cord blood cells, resulting in incrementation of the adhesion cells, in which endothelial nitric oxide synthase and kinase insert domain-containing receptor were positive. Moreover, the mixture of VEGF and TPO increased the CD31^bright cell population when compared with VEGF alone or the mixture of VEGF and stem cell factor. These data suggest that TPO is an important growth factor that can promote endothelial precursor cells expansion ex vivo.

Received for publication, May 14, 2007 , and in revised form, September 5, 2007.

^* This work was supported in part by a grant-in-aid for health and labor science research from the Japanese Ministry of Health, Labor, and Welfare, and in part by a grant-in-aid for Research on Health Sciences focusing on Drug Innovation from the Japan Health Sciences Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-3-3700-9064; Fax: 81-3-3707-6950; E-mail: yamaguch{at}nihs.go.jp.

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