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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 (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 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 Yokoyama, Y. Articles by Chiba, S. Search for Related Content PubMed PubMed Citation Articles by Yokoyama, Y. Articles by Chiba, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2008 Accepted March 5, 2009 Derivation of functional mature neutrophils from human embryonic stem cells Yasuhisa Yokoyama, Takahiro Suzuki, Mamiko Sakata-Yanagimoto, Keiki Kumano, Katsumi Higashi, Tsuyoshi Takato, Mineo Kurokawa, Seishi Ogawa, and Shigeru Chiba* Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital, Tokyo, Japan Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Department of Clinical and Experimental Hematology, University of Tsukuba, Ibaraki, Japan Department of Clinical Hematology, School of Health Sciences, Kyorin University, Tokyo, Japan Division of Tissue Engineering, University of Tokyo Hospital, Tokyo, Japan The 21st Century COE Program, Graduate School of Medicine, University of Tokyo Hospital, Tokyo, Japan * Corresponding author; email: schiba-tky{at}umin.net. Human embryonic stem cells (hESC) proliferate infinitely and are pluripotent. Only a few reports, however, describe specific and efficient methods to induce hESC 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 hESC to differentiate into mature neutrophils. Embryoid bodies were formed with bone morphogenic protein-4, stem cell factor (SCF), Flt-3 ligand (FL), interleukin (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) showed superoxide production, phagocytosis, bactericidal activity, and chemotaxis similar to peripheral blood neutrophils from normal 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. 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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