ACCELERATED RECOVERY OF IRRADIATION-INDUCED BONE-MARROW DEPRESSION BYFIBROBLAST-MEDIATED INTERLEUKIN-6 GENE-THERAPY IN COMBINATION WITH BONE-MARROW TRANSPLANTATION IN MICE

Background. Both fibroblast-mediated cytokine gene therapy and bone ma rrow transplantation (BMT) have proven to be efficient protocols for t he recovery of bone marrow depression. In this report, the effects of fibroblast-mediated interleukin (IL)-6 gene therapy, in combination wi th BMT, on the recovery of irradiation-induced bone marrow depression were investigated, Methods. NIH3T3 fibroblast cells engineered to secr ete IL-6 (NIH3T3-IL-6) or NIH3T3 cells transduced with the neomycin ge ne (NIH3T3-Neo), in combination with 10(7), 10(6), or 10(5) syngeneic bone marrow cells, were implanted into irradiated mice, Results, The p latelets and white blood cells in the peripheral blood of the irradiat ed mice increased greatly 12 days after implantation of NIH3T3-IL-6 ce lls and BMT, the white blood cell counts were restored to a normal lev el 32 days after the combined therapy, and the platelet number was obv iously higher than that in mice implanted with NIH3T3-Neo and BMT. Twe nty and 25 days after the combined therapy, the mice showed accelerate d recovery of colony-forming unit (CFU)-granulocyte/macrophages and CF U-megakaryocytes when compared with the mice implanted with NIH3T3-Neo cells and BMT. Ten days after lethal irradiation with gamma rays, the spleens formed more CFU-spleen in mice implanted with NIH3T3-IL-6 cel ls and BMT than in mice injected with phosphate-buffered saline or NIH 3T3-Neo cells, Combined therapy with NIH3T3-IL-6 cell implantation and BMT delayed the survival period of the hematopoietic-depressed mice s ignificantly when compared with therapy with NIH3T3-Neo cell implantat ion and BMT. Conclusions. These data demonstrated that the combined th erapy of fibroblast-mediated IL-6 gene therapy and BMT could significa ntly promote the recovery of irradiation-induced hematopoietic depress ion.