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Murine Marrow Stromal Response to Myelotoxic Agents in vitro
Author(s) -
Hauser Simon P.,
Udupa Kodetthoor B.,
Lipschitz David A.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1959.x
Subject(s) - stromal cell , haematopoiesis , bone marrow , antimetabolite , stroma , progenitor cell , cell culture , chemistry , cfu gm , cancer research , stem cell , biology , immunology , methotrexate , microbiology and biotechnology , genetics , immunohistochemistry
Previous studies have shown that the haemopoietically active murine long‐term bone marrow culture (LTBMC) is a useful model for studying drug‐induced suppression and recovery of myelopoiesis. We studied the effects on stromal morphology and stromal progenitors, assessed as colony forming unit‐fibroblasts (CFU‐F), of the addition of either the antimetabolite methotrexate (MTX) or the betalactam ceftazidime (CEF) to LTBMC. The examination of 500 μg/ml CEF‐treated cultures revealed a stroma that appeared empty, with modest reduction in total stromal counts, and significant decreases in fat‐containing and endothelial cells. In contrast, treatment with 1 μ M MTX for 1 week initially caused minimal morphologic stromal changes, thereafter total stromal cell count as well as fibroblastoid, endothelial, fat containing and macrophage cells significantly increased. Haemopoiesis and the stroma recovered. Both CEF and MTX reversibly suppressed stromal progenitor cells in LTBMC. When added directly to CFU‐F cultures, the concentrations resulting in a 50% colony growth inhibition were 214 μg/ml for CEF and 375 n M for MTX. These results suggest that CEF, but not MTX, has direct toxic effects on the stroma of established LTBMC. Stromal cell increase following MTX treatment probably indicates a stromal response that may contribute to haemopoietic cell recovery.