Evaluation of chemosensitivity of human bone marrow stromal cells--differences between common chemotherapeutic drugs.
BACKGROUND
Bone marrow stromal cells (BMSCs) are essential for normal hematopoiesis, but also support the growth and survival of malignant hematopoietic cells. There are currently no data available regarding the sensitivity of BMSCs to cytotoxic drugs widely used in the therapy of hematological diseases such as multiple myeloma or acute leukemia.


METHODS
The chemosensitivity of the BMSC line HS-5 and of primary BMSCs from patients were evaluated in comparison to NCI-H929 myeloma and U937 leukemia cells.


RESULTS
Both HS-5 cells and human BMSCs showed substantial cell death in response to chemotherapy. While alkylating agents (melphalan, treosulfan) and doxorubicin demonstrated marked BMSC toxicity, nucleotide analogs (gemcitabine, cytarabine) induced only limited BMSC apoptosis.


CONCLUSIONS
Our data suggest that the BMSC toxicity of cytotoxic compounds should be considered in chemotherapeutic regimens.
Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum der Universität München, Munich, Germany. ralf.schmidmaier@med.uni-muenchen.de
Ralf
R
Schmidmaier
Philipp
P
Baumann
Bertold
B
Emmerich
Gerold
G
Meinhardt
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002066:Busulfan / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects; D020298:U937 Cells; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003561:Cytarabine; D003841:Deoxycytidine; D004317:Doxorubicin; C018404:treosulfan; D002066:Busulfan; D008558:Melphalan; D000093542:Gemcitabine