Sensitivity of mesenchymal stem cells and their progeny to medicines used for the treatment of hematoproliferative diseases.
OBJECTIVE
The influence of cytostatic medicines on mesenchymal stem cells (MSC) and their progeny, fibroblastic colony-forming units (CFU-F), was investigated.


METHODS
Mice were treated with busulfan, cyclophosphamide, cytarabine, methotrexate and bortezomib, as used in clinical practice. MSC and CFU-F were analyzed 3 days and 6 weeks after the treatment termination. To estimate MSC numbers, the ectopic foci formation method was used. Briefly, a donor bone marrow plug was transplanted under the renal capsule of a syngeneic animal, leading to ectopic foci formation. The systemic response of the hematopoietic microenvironment to these drugs was studied using the same method applied to recipients pretreated with the medicines.


RESULTS
CFU-F concentration was halved in the bone marrow of mice treated with busulfan, methotrexate and cyclophosphamide, and was not restored for the next 6 weeks. Proliferative potential and differentiation abilities of MSC were not affected by these medicines. The enlargement of foci size in mice treated with cytostatic agents was not conditioned by MSC, but by more mature stromal precursor cells.


CONCLUSIONS
Cytostatic medicines affect stromal precursors in 2 ways: they decrease CFU-F concentration in the 'steady-state' bone marrow, while stimulating growth of the stromal microenvironment during its de novo formation. MSC are not sensitive to the cytostatic agents used.
Nifontova
Irina
I
National Hematology Research Centre, Moscow, Russian Federation.
Svinareva
Daria
D
Petrova
Tatiana
T
Drize
Nina
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D001897:Boronic Acids; D000069286:Bortezomib; D002066:Busulfan; D003520:Cyclophosphamide; D003561:Cytarabine; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008727:Methotrexate; D051379:Mice; D008815:Mice, Inbred Strains; D011719:Pyrazines; D017154:Stromal Cells / Q000187:drug effects
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D003561:Cytarabine; D000069286:Bortezomib; D003520:Cyclophosphamide; D002066:Busulfan; D008727:Methotrexate