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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6584-6592. Prepublished online as a Blood First Edition Paper on March 25, 2009; DOI 10.1182/blood-2008-06-160838. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-06-160838v1 113/26/6584    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 Google Scholar Articles by Yokoyama, Y. Articles by Chiba, S. PubMed PubMed Citation Articles by Yokoyama, Y. Articles by Chiba, S. Related Collections Hematopoiesis and Stem Cells Phagocytes, Granulocytes, and Myelopoiesis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Derivation of functional mature neutrophils from human embryonic stem cells Yasuhisa Yokoyama13, Takahiro Suzuki1,2,4, Mamiko Sakata-Yanagimoto13, Keiki Kumano1,2, Katsumi Higashi5, Tsuyoshi Takato4, Mineo Kurokawa2, Seishi Ogawa1,4,6, and Shigeru Chiba1,3 1 Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital, Tokyo; 2 Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo; 3 Department of Clinical and Experimental Hematology, University of Tsukuba, Ibaraki; 4 Divison of Tissue Engineering, University of Tokyo Hospital, Tokyo; 5 Department of Clinical Hematology, School of Health Sciences, Kyorin University, Tokyo; and 6 The 21st Century COE Program, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Human embryonic stem cells (hESCs) proliferate infinitely and are pluripotent. Only a few reports, however, describe specific and efficient methods to induce hESCs to differentiate into mature blood cells. It is important to determine whether and how these cells, once generated, behave similarly with their in vivo–produced counterparts. We developed a method to induce hESCs to differentiate into mature neutrophils. Embryoid bodies were formed with bone morphogenic protein-4, stem cell factor (SCF), Flt-3 ligand (FL), interleukin-6 (IL-6)/IL-6 receptor fusion protein (FP6), and thrombopoietin (TPO). Cells derived from the embryoid bodies were cultured on a layer of irradiated OP9 cells with a combination of SCF, FL, FP6, IL-3, and TPO, which was later changed to granulocyte–colony-stimulating factor. Morphologically mature neutrophils were obtained in approximately 2 weeks with a purity and efficiency sufficient for functional analyses. The population of predominantly mature neutrophils (hESC-Neu's) showed superoxide production, phagocytosis, bactericidal activity, and chemotaxis similar to peripheral blood neutrophils from healthy subjects, although there were differences in the surface antigen expression patterns, such as decreased CD16 expression and aberrant CD64 and CD14 expression in hESC-Neu's. Thus, this is the first description of a detailed functional analysis of mature hESC-derived neutrophils. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Functional neutrophils from human ES cells Colin L. Sweeney and Harry L. Malech Blood 2009 113: 6503-6505. [Full Text] [PDF] This article has been cited by other articles: D. S. Kaufman Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells Blood, October 22, 2009; 114(17): 3513 - 3523. [Abstract] [Full Text] [PDF] C. L. Sweeney and H. L. Malech Functional neutrophils from human ES cells Blood, June 25, 2009; 113(26): 6503 - 6505. [Full Text] [PDF]

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