SEARCH:   Advanced

This Article Full Text (PDF) 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 Siena, S. Articles by Moore, M. A. Search for Related Content PubMed PubMed Citation Articles by Siena, S. Articles by Moore, M. A. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Effects of in vitro purging with 4-hydroperoxycyclophosphamide on the hematopoietic and microenvironmental elements of human bone marrow S Siena, H Castro-Malaspina, SC Gulati, L Lu, MO Colvin, BD Clarkson, RJ O'Reilly and MA Moore We describe the effects of 4-hydroperoxycyclophosphamide (4-HC) on the hematopoietic and stromal elements of human bone marrow. Marrow cells were exposed to 4-HC and then assayed for mixed (CFU-Mix), erythroid (BFU-E), granulomonocytic (CFU-GM), and marrow fibroblast (CFU-F) colony-forming cells and studied in the long-term marrow culture (LTMC) system. The inhibition of colony formation by 4-HC was dose and cell- concentration dependent. The cell most sensitive to 4-HC was CFU-Mix (ID50 31 mumol/L) followed by BFU-E (ID50 41 mumol/L), CFU-GM (ID50 89 mumol/L), and CFU-F (ID50 235 mumol/L). In LTMC, a dose-related inhibition of CFU-GM production was noted. Marrows treated with 300 mumol/L 4-HC were completely depleted of CFU-GM but were able to generate these progenitors in LTMC. Marrow stromal progenitors giving rise to stromal layers in LTMC, although less sensitive to 4-HC cytotoxicity, were damaged by 4-HC also in a dose-related manner. Marrows treated with 4-HC up to 300 mumol/L, gave rise to stromal layers composed of fibroblasts, endothelial cells, adipocytes, and macrophages. Cocultivation experiments with freshly isolated autologous hematopoietic cells showed that stromal layers derived from 4-HC- treated marrows were capable of sustaining the long-term production of CFU-GM as well as controls. In conclusion: (1) Hematopoietic progenitors cells, CFU-Mix, BFU-E, and CFU-GM, are highly sensitive to 4-HC, whereas marrow stromal progenitor cells are relatively resistant. (2) Marrows treated with 300 mumol/L 4-HC that are depleted of CFU-Mix, BFU-E, and CFU-GM can generate CFU-GM in LTMC, suggesting that most primitive hematopoietic stem cells (not represented by CFU-Mix) are spared by 4-HC up to this dose. (3) Consequently, the above colony assays are not suitable tools for predicting pluripotent stem cell survival after 4-HC treatment in vitro. Volume 65, Issue 3, pp. 655-662, 03/01/1985 Copyright © 1985 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: I. Angulo, F. G. de las Heras, J. F. Garcia-Bustos, D. Gargallo, M. A. Munoz-Fernandez, and M. Fresno Nitric oxide-producing CD11b+Ly-6G(Gr-1)+CD31(ER-MP12)+ cells in the spleen of cyclophosphamide-treated mice: implications for T-cell responses in immunosuppressed mice Blood, January 1, 2000; 95(1): 212 - 220. [Abstract] [Full Text] [PDF]

	Copyright © 1985 by American Society of Hematology         Online ISSN: 1528-0020