title: Transduction of mesenchymal stem cells with multidrug resistance gene provides protection for bone marrow toxicity after being transplanted into a nude mice model.
abstract: 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-Co(60) 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-Co(60). 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Human P-MSCs moderated by mdr1 gene when transplanted into nude mice may provide chemoprotection for hematopoietic toxicity.
authors.affiliation: Department of Obstetrics and Gynecology, Jilin University, Changchun, Jilin, China.
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Han
authors.forename: Ya-ping
authors.initials: YP
authors.lastname: Li
authors.forename: Ming-zhu
authors.initials: MZ
authors.lastname: Ye
authors.forename: Bo-wei
authors.initials: BW
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Shu-hua
authors.initials: SH
authors.lastname: Zhao
authors.forename: He-lian
authors.initials: HL
authors.lastname: Li
mesh_terms: D000818:Animals; D001853:Bone Marrow; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D019450:Genes, MDR / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010920:Placenta / Q000166:cytology; D011247:Pregnancy
chemical_list: D006454:Hemoglobins; D049452:Green Fluorescent Proteins