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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 (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 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 Social Bookmarking                   What's this? Submitted April 25, 2002 Accepted July 18, 2002 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 Stem Cell Biology Laboratory, NIDDK-Navy Transplantation and Autoimmunity Branch, Bethesda, MD, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA Stem Cell Biology Laboratory, NIDDK-Navy Transplantation and Autoimmunity Branch, Bethesda, MD, USA Office of the Chief Medical Examiner, Baltimore, MD, USA Large Scale Biology Corp., Vacaville, CA, USA Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA * Corresponding author; email: john.chute{at}lsbc.com. Adult human bone marrow (ABM) is an important source of hematopoietic stem cells for transplantation in the treatment of malignant and non-malignant diseases. However, unlike the recent progress which 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 utilizing human brain endothelial cells (HUBEC) which supports the quantitative expansion of the most primitive measurable cell within the adult bone marrow compartment, the NOD/SCID repopulating cell (SRC). Co-culture of human ABM CD34+ cells with brain endothelial cells for 7 days supported a 5.4 fold increase in CD34+ cells, induced >95% of the CD34+CD38- subset to enter cell division, and produced progeny which engrafted NOD/SCID mice at significantly higher rates than fresh ABM CD34+ cells. Using a limiting dilution analysis, we found the frequency of SRC within fresh ABM CD34+ cells to be 1 in 9.9 x 105 cells. Following HUBEC culture, the estimated frequency of SRC increased to 1 in 2.4 x 105 cells. All mice transplanted with HUBEC-cultured cells showed B lymphoid and myeloid differentiation, indicating that a primitive hematopoietic cell was preserved during culture. Non-contact HUBEC cultures also maintained SRC 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 which increases the repopulating capacity of adult human bone marrow. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. 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