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Titolo:
Bone marrow stromal dysfunction in mice administered cytosine arabinoside
Autore:
Ben-Ishay, Z; Barak, V;
Indirizzi:
Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Anat & Cell Biol, IL-91010 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91010 -91010 Jerusalem, Israel Hadassah Med Ctr, Dept Oncol, Immunol Lab Tumor Diag, IL-91120 Jerusalem, Israel Hadassah Med Ctr Jerusalem Israel IL-91120 g, IL-91120 Jerusalem, Israel
Titolo Testata:
EUROPEAN JOURNAL OF HAEMATOLOGY
fascicolo: 4, volume: 66, anno: 2001,
pagine: 230 - 237
SICI:
0902-4441(200104)66:4<230:BMSDIM>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; BASEMENT-MEMBRANE COMPONENTS; PROGENITOR CELLS; PERIPHERAL-BLOOD; IN-VITRO; DIRECT-CONTACT; CYTOKINE EXPRESSION; NORMAL DONORS; SERUM LEVELS;
Keywords:
bone marrow stroma; cytosine arabinoside (Ara-C); induced damage; contact and non-contact co-culture; CFU-F; HPPC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Ben-Ishay, Z Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Anat & Cell Biol, IL-91010 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91010 lem, Israel
Citazione:
Z. Ben-Ishay e V. Barak, "Bone marrow stromal dysfunction in mice administered cytosine arabinoside", EUR J HAEMA, 66(4), 2001, pp. 230-237

Abstract

Objective. The aim of the study was to investigate ex-vivo the bone marrow(BM) stroma of mice under conditions of low- and high-dose cytosine arabinoside (Ara-C), a cycle-specific drug (S-phase) and to assess possible stromal damage, apart from the killing of hematopoietic cells. Stroma consists of mesenchymal elements generally not in the cell cycle; therefore it. couldnot be a target for the killing effect of Ara- C. Materials and Methods. The stromal function was studied by tile following: the incidence of stromalstem cells, i.e. CFU-F; formation of stromal layers under growth conditions of long-term culture (LTC) followed by irradiation and overlayering of test cells in contact and noncontact co-cultures; subsequent culture of the test cells in a semi-solid medium to assay the incidence of hyperproliferative potential cells (HPPC); production of GM-CSF, IL-3, IL-4, IL-6 and IFN gamma in the conditioned medium (CM) of confluent stromal layers. All tests and assays were carried out on BM specimens, 1-4 d after Ara-C administration and on controls. Results. Low-dose Ara-C induces a marked decrease of CFU-F, compensated by cycle induction of pre-CFU-F, young-type stromal stem cells. High-dose Ara-C causes a CFU-F decrease to almost zero level. The time length to layer confluency is normal after low-dose Ara-C (similar to 10 d) and prolonged after a high dose (similar to 30 d). The confluent layers from mice receiving low- or high-dose Ara-C support hematopoiesis adequately. Among the growth factors and: cytokines assayed, only IL-6 is detected in CM layers. IL-6 decreases after a low dose of Ara-C and increases after ahigh dose. The cause of IL-6 fluctuations is yet to be investigated. It is, however, evident that IL-6 is not an essential factor in support of hematopoiesis. Conclusions. Taken together, the current study in mice indicates that Ara-C administration, in particular a high dose, induces bone marrow stromal damage and/or disfunction. The long period of time to roach layer confluency after a high Ara-C dose might reflect the in-vivo situation of slow stromal regeneration.

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Documento generato il 02/04/20 alle ore 18:15:58