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The Effects Of IL-2 On The Hematopoiesis And Immune Status In The Lethally Irradiated Mice Transplanted With The Hematopoietic Stem Cells

Posted on:2003-04-26Degree:MasterType:Thesis
Country:ChinaCandidate:Q MaFull Text:PDF
GTID:2144360065960860Subject:General surgery
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Objective High-dose chemotherapy or radiotherapy followed by hematopoietic stem cells transplantation (HSCT) is introduced more and more in the remedy for stage III or IV cancer , especially the solid cancer. Although the mortality of HSCT has gradually decreased as a result of the development of the skill, the hematopoiesis and immune status is still an important factor in threatening the patient's life. In this study, a model was formed with BALB/c mice on peripheral blood stem cell transplantation. Interleukin-2 was chosen for posttransplantation treatement, for the purpose of observing whether Interleukin-2 could accelerate the recovery of the hematopoiesis and immune status after the transplantation. Material and Methods Donor BALB/c mice were treated with Cyclophosphamide at 200mg/kg intraperitoneally on 5 days before the study and Filgrastim at 250ug/kg daily subcutaneously on 3 days, 2 days , 1 day before the study and the very day of the study. The whole blood was collected 2 to 3 hours after the last injection of Filgrastim, and peripheral blood mononuclear cell (MNC) suspension was harvested after separation of blood over Ficoll-hypaque gradient ( p = 1.090 ). Another group of 40 BALB/c mice were given a leathal dose ( 8 Gy ) of total body irradiation by 60Co Y rays on the very day of the study.All the mice were randomly divided into four groups, ten mice in every group. Among them , one group were treated as single irradiation group , the other mice received 0.5 x 106 MNCs via the tail vein in 4 to 6 hours posttransplantation. After the transplantation, the groups were treated in different ways. Group A, i.e. single irradiation group, wasn't treated with any special measurement. Group B, i.e. Filgrastim group, was treated with Filgrastim at 200[ig/kg subcutaneously. Group C, i.e. Interleukin-2 group, was treated with Interleukin-2 at 2.5 x 106 lU/kg intraperitoneally. Group D, i.e. Filgrastim + Interleukin-2 group, was treated with both Filgrastim at 200ug/kg subcutaneously and Interleukin-2 at 2.5 x 106 lU/kg intraperitoneally. The complete blood cell count was performed per week after the transplantation in this study. From the fourth week, the ratio of CD4+/CD8+ cells was detected every other week. In the end of the study, the bone marrow specimens were collected from the experiment mice and the normal mouse, and sectioned into superthin pieces, then observed under the transmission electron microscope (TEM). At the same time, the colony forming unit of granulocyte-macrophage (CFU-GM) in the bone marrow were tested. The spleens were weighed and counted the colony forming unit (CFU-S). Results (1) All ten mice in the single irradiation group were died in about 2 weeks after the irradiation. The survival rate was significantly higher in the transplantation groups than in the single irradiation group, but no significant difference was seen between the each transplantation group. (2) The white blood cell count dropped rapidly after the irradiation, andfell down to the bottom on day 7 to 14, then increased slowly. But the recovery speed of each group is different, the Filgrastim group and the Filgrastim + Interleukin-2 group show a faster recovery than that of the Interleukin-2 group. There is no difference between the Filgrastim group and the Filgrastim + Interleukin-2 group. (3) After the transplantation, it was found that IL-2 injection could accelerate the recovery of the ratio of CD4+/CD8+ cells from peripheral lymphocytes. (4) The TEM results revealed that the endothelicytes and reticulocytes in the bone marrow of the normal mouse had an integrate structure, and there was a solid contact between the two kinds of cells and the hematopoietic stem cells. The two kinds of cells in the bone marrow of the single irradiation group showed some change of impairment: vesication or necrosis of the mitochondrion, swelling of the reticulum endoplasmic, discontinuity of the nuclear membrane, increase of the liposome, and a loose contact with the stem cells. The transplantation groups...
Keywords/Search Tags:Interleukin-2, hematopoietic stem cells, transplantation, mice, the function of the hematopoiesis and immune, granulocyte colony-stimulating factor
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