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Blood, 1 June 2008, Vol. 111, No. 11, pp. 5298-5306. Prepublished online as a Blood First Edition Paper on April 3, 2008; DOI 10.1182/blood-2007-10-117622. This Article Full Text Full Text (PDF) Supplemental Figures and Video All Versions of this Article: blood-2007-10-117622v1 111/11/5298    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Takayama, N. Articles by Nakauchi, H. Search for Related Content PubMed PubMed Citation Articles by Takayama, N. Articles by Nakauchi, H. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors Naoya Takayama1, Hidekazu Nishikii1, Joichi Usui1, Hiroko Tsukui1, Akira Sawaguchi2, Takashi Hiroyama3, Koji Eto1, and Hiromitsu Nakauchi1 1 Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo; 2 Department of Anatomy, University of Miyazaki Faculty of Medicine, Miyazaki; and 3 Cell Engineering Division, Rikagaku Kenkyusho (RIKEN) BioResource Center, Tsukuba, Japan Human embryonic stem cells (hESCs) could potentially represent an alternative source for blood transfusion therapies and a promising tool for studying the ontogeny of hematopoiesis. When we cultured hESCs on either C3H10T1/2 or OP-9 cells to facilitate hematopoiesis, we found that exogenous administration of vascular endothelial growth factor promoted the emergence of sac-like structures, which we named embryonic stem cell–derived sacs (ES-sacs). These ES-sacs consisted of multiple cysts demarcated by cellular monolayers that retained some of the properties of endothelial cells. The spherical cells inside ES-sacs expressed primarily CD34, along with VE-cadherin, CD31, CD41a, and CD45, and were able to form hematopoietic colonies in semisolid culture and to differentiate into mature megakaryocytes by day 24 in the presence of thrombopoietin. Apparently, ES-sacs provide a suitable environment for hematopoietic progenitors. Relatively large numbers of mature megakaryocytes could be induced from the hematopoietic progenitors within ES-sacs, which were then able to release platelets that displayed integrin IIbβ3 activation and spreading in response to ADP or thrombin. This novel protocol thus provides a means of generating platelets from hESCs, which could serve as the basis for efficient production of platelets for clinical transfusion and studies of thrombopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Yokoyama, T. Suzuki, M. Sakata-Yanagimoto, K. Kumano, K. Higashi, T. Takato, M. Kurokawa, S. Ogawa, and S. Chiba Derivation of functional mature neutrophils from human embryonic stem cells Blood, June 25, 2009; 113(26): 6584 - 6592. [Abstract] [Full Text] [PDF] F. Timmermans, I. Velghe, L. Vanwalleghem, M. De Smedt, S. Van Coppernolle, T. Taghon, H. D. Moore, G. Leclercq, A. W. Langerak, T. Kerre, et al. Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones J. Immunol., June 1, 2009; 182(11): 6879 - 6888. [Abstract] [Full Text] [PDF] K.-D. Choi, J. Yu, K. Smuga-Otto, G. Salvagiotto, W. Rehrauer, M. Vodyanik, J. Thomson, and I. Slukvin Hematopoietic and Endothelial Differentiation of Human Induced Pluripotent Stem Cells Stem Cells, March 1, 2009; 27(3): 559 - 567. [Abstract] [Full Text] [PDF] N. Takayama, K. Eto, H. Nakauchi, and S. Yamanaka Generation of Blood Cells from Human Ips Cells in Vitro through the Hematopoietic Progenitors Concentrated within the Unique Structures, Ips-Sac. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1992 - 1992. [Abstract]

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