ヒト骨髄間質細胞に関する研究　第1編 ヒト骨髄間質細胞の増殖動態並びに造血支持能に及ぼす抗白血病剤の影響

The effects of antileukemic agents on the growth of human bone marrow stromal cells (HBMSC) and its ability to sustain the growth of normal hematopoietic progenitors were studied by using a modified Dexter's culture system. Antileukemic agents used were daunor-ubicin (DNR), doxorubicin (DXR), mitoxantron (MIT), aclarubicin (ACR), vincristine (VCR), cyclophosphamide (CPM), cytosine arabinoside (ara-C) and methotrexate (MTX). In this experiment, HBMSC were exposed to each concentration of DNR, DXR, MIT, ACR, VCR and CPM for 3 hours, and to ara-C and MTX for 7 days. DNR, DXR, MIT and ACR suppressed the growth of HBMSC at the concentration of ≧10(-6)M, and also suppressed its ability to sustain the growth of normal hematopoietic progenitors at the concentration of ≧10(-7)M. VCR suppressed both the growth of HBMSC and its ability to sustain the growth of normal hematopoietic progenitors at the concentration of and also suppressed its ability to suatain the growth of norwth hematopoietic progenitors at the concentration of ≧10(-7)M. CPM suppressed the growth of HBMSC at the concentration of >10(-4)M. However, its ability to sustain the growth of normal hematopoietic progenitors was not suppressed. Ara-C and MTX did not suppress the growth of HBMSC at the concentration of 10(-8)M to 10(-3)M. The ability of HBMSC to sustain the growth of normal hematopoietic progenitors was not suppressed by Ara-C. On the other hand, it was suppressed by MTX of >10(-4)M. These findings, which clarified the effects of the antileukemic agents on the functions of HBMSC, provide some information not only on the optimal combination of antileukemic agents and premedication of bone marrow transplantation, but also on drug-induced hematotoxicity.

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