Augmentation of hematopoiesis by fibroblast-mediated interleukin-6 gene therapy in mice with chemotherapy.
Murine fibroblast NIH3T3 cells engineered to secrete interleukin-6 (NIH3T3-IL-6) were implanted intraperitoneally into mice and observed for their hematopoietic effects with or without 5-fluorouracil (5-FU) administration. In normal mice, the platelet and neutrophil counts in peripheral blood increased significantly after implantation of NIH3T3-IL-6 cells, but the total white blood cell numbers showed no obvious elevation. The granulocyte-macrophage colony-forming unit (CFU-GM) and megakaryocyte colony-forming unit (CFU-MK) numbers formed by stem cells in bone marrow and spleen were also found to be significantly increased after implantation of NIH3T3-IL-6 cells when compared with those in mice after implantation of NIH3T3 cells transduced with neomycin gene (NIH3T3-Neo). To observe the protective effects of NIH3T3-IL-6 cells on hematopoietic depression in chemotherapy-treated mice, the mice were preinjected with 5-FU at a dosage of 150 mg/kg before implantation of NIH3T3-IL-6 cells. The platelet and neutrophil counts showed accelerated recovery after implantation of NIH3T3-IL-6 cells. The numbers of CFU-GM and CFU-MK in bone marrow and spleen were also found to be markedly increased in hematopoietic-depressed mice when compared with those in mice implanted with NIH3T3-Neo cells. These data suggest that fibroblast-mediated IL-6 gene therapy, which can augment hematopoiesis in mice with or without chemotherapy, will be of great help in the recovery from hematopoietic depression after chemotherapy.
Cao
X
X
Department of Immunology, Second Military Medical University, Shanghai, P.R. China. cxt@ecmu.ihep.ac.cn
Cai
R
R
Ju
D W
DW
Tao
Q
Q
Yu
Y
Y
Wang
J
J
D016475:3T3 Cells; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D017690:Cell Transplantation; D004353:Drug Evaluation, Preclinical; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005720:Gamma Rays; D015316:Genetic Therapy; D006410:Hematopoiesis / Q000187:drug effects* / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010976:Platelet Count / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D015850:Interleukin-6; D005472:Fluorouracil