Sensitivity of Mesenchymal Stem Cells and Their Progeny to Medicines Used for the Treatment of Hematoproliferative Diseases

Abstract

Background/Aims: 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.

Ganoderma spore lipid protects mouse bone marrow mesenchymal stem cells and hematopoiesis from the cytotoxicity of the chemotherapeutic agent

“…MSCs have the expansion capacity, but the capacity is severely impaired in patients receiving high‐dose chemotherapy . The chemotherapy‐induced decrease in MSC expansion may result from a reduction of CFU‐forming frequency, a reduction in MSC proliferation, and an increase in MSC apoptosis . Our in vitro experiment demonstrated that CTX treatment damaged the typical morphology of MSCs and induced an impaired proliferation and an increased apoptosis in MSCs as evidenced by MTT and Annexin/PI assay, which are consistent with findings from other studies .…”

Human amniotic fluid stem cells protect rat lungs exposed to moderate hyperoxia

“…It is worth noting that thanks to the low expression of HLA‐DR these cells may trigger a lower immune‐response, which was also confirmed by the absence of inflammatory areas in the recipients. For this reason we then decided to avoid the immunosuppressant drugs, to preclude interference in stem cell activity . In addition the low immune‐response and the reported absence of tumorigenesis justify in our experimental design the preclusion of a specific control group in healthy animals administrated with hAFS cells …”

In Vitro and In Vivo Cardiomyogenic Differentiation of Amniotic Fluid Stem Cells

“…To analyze the AFS cells in vivo potential, here we preferred to avoid the use of immunosuppressant drugs, as several controversial results have been recently reported regarding their influence on stem cells differentiation potential [61][62][63]. In this work a marked cellular response characterized by an infiltration of T-cells, NK cells and macrophages occurs in transplanted animals, independently from the presence or absence of the I/R injury.…”