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

摘要Background Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs.The human multidrug resistance (mdr1) 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 mdr1 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 mdr1 gene and green fluorescent protein (GFP) reporter gene.The integration and expression of mdr1 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 mdr1-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.Reeults After PAC treatment,mdr1-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 mdr1-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).Conclusion Human P-MSCs moderated by mdr1 gene when transplanted into nude mice may provide chemoprotection for hematopoietic toxicity.

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作者单位 Department of Obstetrics and Gynecology, Second Hospital, Jilin University, Changchun, Jilin 130041, China [1] Department of Ophthalmology, Second Hospital, Jilin University,Changchun, Jilin 130041, China [2] Department of Obstetrics and Gynecology, Zhongshan Hospital,Xiamen University, Xiamen, Fujian 361004, China [3]
栏目名称 ORIGINAL ARTICLES
DOI 10.3760/cma.j.issn.0366-6999.2012.18.009
发布时间 2013-01-25
基金项目
This study was supported by a grant from the National Natural Science Foundation of China
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中华医学杂志(英文版)

中华医学杂志(英文版)

2012年125卷18期

3246-3250页

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