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Blood, 15 January 2005, Vol. 105, No. 2, pp. 576-583. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-04-1467. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1467v1 105/2/576    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 Chute, J. P. Articles by Oxford, C. Search for Related Content PubMed PubMed Citation Articles by Chute, J. P. Articles by Oxford, C. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38– cells and SCID-repopulating cells John P. Chute, Garrett G. Muramoto, Jennifer Fung, and Carol Oxford From the Stem Cell Biology Laboratory, Large Scale Biology Corporation, Vacaville, CA; Division of Cellular Therapy, Duke University, Durham, NC; The Jackson Laboratories, Sacramento, CA; and Department of Pathology, UC Davis, Davis, CA. The CD34+CD38– phenotype identifies a population in the bone marrow that is enriched in the steady state for hematopoietic stem cells (HSCs). Following ex vivo culture of CD34+ cells, HSC content is difficult to measure since committed CD34+CD38+ progenitors down-regulate CD38 surface expression during culture. In this study, we sought to define the phenotype of human HSCs following ex vivo culture under conditions that support the expansion of human cells capable of repopulating non-obese diabetic/severe combined immunodeficiency (SCID)–repopulating cells (SRCs). Contact coculture of fluorescence-activated cell sorter (FACS)–sorted bone marrow (BM) CD34+CD38– cells with human brain endothelial cells (HUBECs) supported a 4.4-fold increase in CD34+CD38– cells with a concordant 3.6-fold increase in SRCs over 7 days. Noncontact HUBEC cultures and the addition of thrombopoietin, stem cell factor (SCF), and macrophage colony stimulating factor I receptor (Fms)–like tyrosine kinase 3 (Flt-3) ligand supported further increases in CD34+CD38– cells (6.4-fold and 13.1-fold), which correlated with significant increases in SRC activity. Moreover, cell-sorting studies performed on HUBEC-cultured populations demonstrated that SRCs were significantly enriched within the CD34+CD38– subset compared with the CD34–CD38– population after culture. These results indicate that human HSCs can be identified and characterized by phenotype following expansion culture. These studies also demonstrate that HUBEC-elaborated soluble factors mediate a unique and potent expansion of human HSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. B. Salter, S. K. Meadows, G. G. Muramoto, H. Himburg, P. Doan, P. Daher, L. Russell, B. Chen, N. J. Chao, and J. P. Chute Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo Blood, February 26, 2009; 113(9): 2104 - 2107. [Abstract] [Full Text] [PDF] R. Safi, G. G. Muramoto, A. B. Salter, S. Meadows, H. Himburg, L. Russell, P. Daher, P. Doan, M. D. Leibowitz, N. J. Chao, et al. Pharmacological Manipulation of the RAR/RXR Signaling Pathway Maintains the Repopulating Capacity of Hematopoietic Stem Cells in Culture Mol. Endocrinol., February 1, 2009; 23(2): 188 - 201. [Abstract] [Full Text] [PDF] J. P. Chute, G. G. Muramoto, A. B. Salter, S. K. Meadows, D. W. Rickman, B. Chen, H. A. Himburg, and N. J. Chao Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice Blood, March 15, 2007; 109(6): 2365 - 2372. [Abstract] [Full Text] [PDF] J. P. Chute, G. G. Muramoto, J. Whitesides, M. Colvin, R. Safi, N. J. Chao, and D. P. McDonnell Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells PNAS, August 1, 2006; 103(31): 11707 - 11712. [Abstract] [Full Text] [PDF] N. Takebe, X. Cheng, A. M. Farese, E. Welty, B. Meisenberg, and T. MacVittie Human Brain Endothelial Cells (HUBEC) Can Expand Both Human Bone Marrow and Cord Blood SCID-Repopulating Cells (SRC) through Cell Contact Rather Than Soluble Factors. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 36 - 36. [Abstract] R. B. Walter, J. L. Pirga, M. R. Cronk, S. Mayer, F. R. Appelbaum, and D. E. Banker PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism Blood, November 15, 2005; 106(10): 3584 - 3593. [Abstract] [Full Text] [PDF]

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