Centre for Research in Biomedicine, Faculty of Applied Sciences, University of the West of England, Bristol, UK.
Ann Hematol. 2011 Jul;90(7):777-89. doi: 10.1007/s00277-010-1141-8. Epub 2011 Jan 14.
The adverse effects of melphalan and cyclophosphamide on hematopoietic stem cells are well-known; however, the effects on the mesenchymal stem cells (MSCs) residing in the bone marrow are less well characterised. Examining the effects of chemotherapeutic agents on patient MSCs in vivo is difficult due to variability in patients and differences in the drug combinations used, both of which could have implications on MSC function. As drugs are not commonly used as single agents during high-dose chemotherapy (HDC) regimens, there is a lack of data comparing the short- or long-term effects these drugs have on patients post treatment. To help address these problems, the effects of the alkylating chemotherapeutic agents cyclophosphamide and melphalan on human bone marrow MSCs were evaluated in vitro. Within this study, the exposure of MSCs to the chemotherapeutic agents cyclophosphamide or melphalan had strong negative effects on MSC expansion and CD44 expression. In addition, changes were seen in the ability of MSCs to support hematopoietic cell migration and repopulation. These observations therefore highlight potential disadvantages in the use of autologous MSCs in chemotherapeutically pre-treated patients for future therapeutic strategies. Furthermore, this study suggests that if the damage caused by chemotherapeutic agents to marrow MSCs is substantial, it would be logical to use cultured allogeneic MSCs therapeutically to assist or repair the marrow microenvironment after HDC.
马法兰和环磷酰胺对造血干细胞的不良影响是众所周知的；然而，它们对骨髓中驻留的间充质干细胞（MSCs）的影响还不太清楚。由于患者的变异性和所用药物组合的差异，在体内检查化疗药物对患者 MSCs 的影响非常困难，这两者都可能对 MSC 功能产生影响。由于在大剂量化疗（HDC）方案中药物通常不作为单一药物使用，因此缺乏比较这些药物在治疗后对患者的短期或长期影响的数据。为了帮助解决这些问题，本研究在体外评估了烷基化化疗药物环磷酰胺和马法兰对人骨髓间充质干细胞的影响。在这项研究中，化疗药物环磷酰胺或马法兰暴露于 MSCs 对 MSC 扩增和 CD44 表达有很强的负面影响。此外，MSC 支持造血细胞迁移和再定植的能力也发生了变化。因此，这些观察结果突出了在未来治疗策略中，在化疗预处理的患者中使用自体 MSCs 的潜在缺点。此外，本研究表明，如果化疗药物对骨髓 MSCs 造成的损害很大，那么从逻辑上讲，应该使用培养的同种异体 MSCs 来治疗 HDC 后辅助或修复骨髓微环境。
