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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-04-1238. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1238v1 100/13/4433    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 Davis, T. A. Search for Related Content PubMed PubMed Citation Articles by Chute, J. P. Articles by Davis, T. A. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2002, Vol. 100, No. 13, pp. 4433-4439 HEMATOPOIESIS Ex vivo culture with human brain endothelial cells increases the SCID-repopulating capacity of adult human bone marrow John P. Chute, Abha A. Saini, Dennis J. Chute, Mark R. Wells, William B. Clark, David M. Harlan, Jenny Park, Margaret K. Stull, Curt Civin, and Thomas A. Davis From the Stem Cell Biology Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Navy Transplantation and Autoimmunity Branch, Bethesda, MD; Uniformed Services University of the Health Sciences, Bethesda, MD; Office of the Chief Medical Examiner, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; and Large Scale Biology Corporation, Vacaville, CA. Adult human bone marrow (ABM) is an important source of hematopoietic stem cells for transplantation in the treatment of malignant and nonmalignant diseases. However, in contrast to the recent progress that has been achieved with umbilical cord blood, methods to expand ABM stem cells for therapeutic applications have been disappointing. In this study, we describe a novel culture method that uses human brain endothelial cells (HUBECs) and that supports the quantitative expansion of the most primitive measurable cell within the adult bone marrow compartment, the nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cell (SRC). Coculture of human ABM CD34+ cells with brain endothelial cells for 7 days supported a 5.4-fold increase in CD34+ cells, induced more than 95% of the CD34+CD38 subset to enter cell division, and produced progeny that engrafted NOD/SCID mice at significantly higher rates than fresh ABM CD34+ cells. Using a limiting dilution analysis, we found the frequency of SRCs within fresh ABM CD34+ cells to be 1 in 9.9 × 105 cells. Following HUBEC culture, the estimated frequency of SRCs increased to 1 in 2.4 × 105 cells. All mice that received transplants of HUBEC-cultured cells showed B-lymphoid and myeloid differentiation, indicating that a primitive hematopoietic cell was preserved during culture. Noncontact HUBEC cultures also maintained SRCs at a level comparable to contact HUBEC cultures, suggesting that cell-to-cell contact was not required. These data demonstrate that human brain endothelial cells possess a unique hematopoietic activity that increases the repopulating capacity of adult human bone marrow. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] J. P. Chute, G. G. Muramoto, H. K. Dressman, G. Wolfe, N. J. Chao, and S. Lin Molecular Profile and Partial Functional Analysis of Novel Endothelial Cell-Derived Growth Factors that Regulate Hematopoiesis Stem Cells, May 1, 2006; 24(5): 1315 - 1327. [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] J. P. Chute, G. G. Muramoto, J. Fung, and C. Oxford Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38- cells and SCID-repopulating cells Blood, January 15, 2005; 105(2): 576 - 583. [Abstract] [Full Text] [PDF] J. P. Chute, G. Muramoto, J. Fung, and C. Oxford Quantitative Analysis Demonstrates Expansion of SCID-Repopulating Cells and Increased Engraftment Capacity in Human Cord Blood Following Ex Vivo Culture with Human Brain Endothelial Cells Stem Cells, March 1, 2004; 22(2): 202 - 215. [Abstract] [Full Text] [PDF] W. Li, S. A. Johnson, W. C. Shelley, M. Ferkowicz, P. Morrison, Y. Li, and M. C. Yoder Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro Blood, December 15, 2003; 102(13): 4345 - 4353. [Abstract] [Full Text] [PDF]

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