Transduction of mesenchymal stem cells with multidrug resistance gene provides protection for bone marrow toxicity after being transplanted into a nude mice model

• Published in: Chinese medical journal 2012-09, Vol.125 (18), p.3246-3250
• Main Authors: Han, Li-ying, Li, Ya-ping, Ye, Ming-zhu, Wang, Bo-wei, Wang, Qiang, Zhao, Shu-hua, Li, He-lian
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow; Cell Differentiation - genetics; Cell Differentiation - physiology; Cells, Cultured; Erythrocytes - metabolism; Female; Genes, MDR - genetics; Genes, MDR - physiology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hemoglobins - metabolism; Humans; Leukocytes - metabolism; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Placenta - cytology; Pregnancy; 保护作用; 基因转导; 多药耐药基因; 模型构建; 毒性; 裸鼠; 静脉移植; 骨髓间充质干细胞
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2012.18.009

Background Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance （mdrl） gene is well-known for its ability to confering drug resistance. In this study, we meant to transplant the placenta mesenchymal stem cells （P-MSCs） moderated by mdrl gene into a nude mice model radiated by γ-Co60 and to explore the chemoprotection for bone marrow （BM） toxicity. Methods Human P-MSCs were isolated from trypsin-digested term placentas and then transduced by with reconstructed retroviral vector containing mdrl gene and green fluorescent protein （GFP） reporter gene. The integration and expression of mdrl gene was observed indirectedly by the expression of GFP. A nude mice model was constructed after irradiation with a sublethal dosage of γ-Co60. These irradiated mice were transplanted with mdrl-MSCs through the caudal vein and then received paclitaxel （PAC） intraperitoneal chemotherapy. The Peripheral peripheral blood （PB） of the nude mice was collected, and the PB cells counts and values were determined using an automatic analyzer. Results After PAC treatment, mdrl-MSCs transplanted mice showed markedly improved survival upon compared to MSCs transplanted mice （85.7% vs. 57.1%）. White blood cell （WBC） and red blood cell （RBC） counts as well as the hemoglobin （Hb） values were significantly increased in PAC treated mdrl-MSCs mice compared to PAC treated control mice when PAC chemotherapy had been finished （all P 〈0.05）, but the difference was not found in the plateltes （PLT） count （P 〉0.05）.