Doxorubicin has in vivo toxicological effects on ex vivo cultured mesenchymal stem cells
Doxorubicin has in vivo toxicological effects on ex vivo cultured mesenchymal stem cells
复制标题
DOI：
10.1016/j.toxlet.2013.11.023
复制
发表时间：
2014-01-30
影响因子：
3.5
通讯作者：
Melo, Marilia Martins
中科院分区：
文献类型：
--
作者：
Oliveira, Maira Souza;Carvalho, Juliana Lott;Melo, Marilia Martins
多柔比星是一种有效的化疗药物，可导致心脏毒性。一种替代治疗心脏毒性的方法是自体间充质干细胞（MSCs）移植。目前尚不清楚dox是否对化疗受试者的MSC具有有害作用，因此本研究旨在评价dox对离体培养的MSC的体内毒理学作用，推断自体移植是否可能是暴露于药物的患者的替代治疗。Wistar大鼠接受dox或生理盐水。处理后，处死动物，分离骨髓MSC，表征细胞表面标志物，并根据其活力、碱性磷酸酶产生和增殖动力学进行评估。此外，骨髓间充质干细胞的心脏分化和肌钙蛋白T和连接蛋白43的表达进行了评估。与对照组相比，dox组的未分化MSCs保持了表面标记的模式，并且具有相似的活力结果。相反，他们表现出较低的碱性磷酸酶的生产，增殖率和连接蛋白43的表达。dox组的预处理MSCs显示较低的肌钙蛋白T水平。阿霉素对宿主骨髓间充质干细胞有毒性作用。这一结果使得自体MSC移植治疗心脏毒性的可能性，这可能是接受这种抗氧化剂的受试者的不合适的选择。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Doxorubicin (dox) is an effective chemotherapeutic agent that leads to cardiotoxicity. An alternative treatment for dox-cardiotoxicity is autologous mesenchymal stem cells (MSCs) transplantation. It remains unclear if dox has deleterious effects on MSCs from subjects under chemotherapy, therefore this study aimed to evaluate dox in vivo toxicological effects on ex vivo cultured MSCs, inferring whether autologous transplantation may be an alternative treatment in patients who are exposed to the drug. Wistar rats received either dox or saline. Following treatments, animals were sacrificed and bone marrow MSCs were isolated, characterized for cell surface markers and assessed according to their viability, alkaline phosphatase production, and proliferation kinetics. Moreover, MSCs were primed to cardiac differentiation and troponin T and connexin 43 expressions were evaluated. Compared to control, undifferentiated MSCs from dox group kept the pattern for surface marker and had similar viability results. In contrast, they showed lower alkaline phosphatase production, proliferation rate, and connexin 43 expression. Primed MSCs from dox group showed lower troponin T levels. It was demonstrated a toxic effect of dox in host MSCs. This result renders the possibility of autologous MSCs transplantation to treat dox-cardiotoxicity, which could be a non-suitable option for subjects receiving such antineoplastic agent. (C) 2013 Elsevier Ireland Ltd. All rights reserved.