| ObjectiveTo induce recipient immunologic tolerance response in the xenogeneic bone marrow transplantation (XBMT). And to establishment of a stable and low-level disparate hematopoietic chimerism model in mice-to-rat. So we can study on the effect of the disparate hematopoietic chimerism for preventing graft versus host disease, with using recipient' bone marrow transplant to donor inversely, when the chimera is lower 10 percent. And then observe survival and changes of the new disparate hematopoietic chimerism that formation after inversely bone marrow transplantation. Experimental study the provision to maintaining the new chimerism, and so on.Methods1.Use of various peri- mouse and rat, they are BALB/c and SD and Wister, divide into groups, then development of bone marrow transplantation and others.2. First, SD rats were conditioned with 5.0Gy sub-lethal total body irradiation (TBI), then followed by infusion of BALB/c mice' bone marrow on day 0, they were injected in abdominal cavity with Cytoxan (CTX) 150mg/Kg on day 2. The procedure let SD rats come into being new chimerism and have donor-specific immunologic tolerance.3. Second, BALB/c mice were conditioned with 9.0Gy lethal TBI when the chimerism rate was lower 10% and divided into three groups randomly. Group A was injected with only bone marrow cells 6×107 from normal SD rats. Group B was injected with bone marrow cells 6×107 and spleen cells 2×107from normal SD rats. And group B was injected with bone marrow cells 6×107 and spleen cells 2×107 from chimerical SD rats. Then observed the changes, as for physiological index and chimerism rate and GVHD, and so on, about to exceed 150 days.4. The chimerical BALB/c mice were subsequence injected with only bone marrow cells 8×107 or 1×l08from normal SD rats. Then the lymphoid cells of mice were present in the SD rats detected by fluorescence activated cell sorter (FACS).Results1. Sccessfully induced low-level disparate hematopoietic chimerism it was that SD rat conditioned with 5.0 Gy sub-lethal TBI add on injected in abdominal cavity with CTX 150mg/Kg after 48h in mice to rat in BMT. The evidence is Chromatosome detection and R-PE Mouse anti-mouse H-2Dd by FACS. The chimera rate were 9.4%-23.85%, 1.06%-10.48% on day 30,110 respectively.2. BALB/c mice were conditioned with 9.0Gy lethal TBI, then for a long time without any immunosuppressant, infusion by caudal vein with chimera SD rat bone marrow cells when its chimerism rate was lower 10%. The chimerism rate were 1.17-60.2%, 0.88-2.34% on day 30, 120 respectively.3 Forty-five days after the transplantation, by mixed lymphocyte reaction (MLR) assays. The response of BALB/c mice spleen cells to chimera SD rat spleen cells and normal SD rat 'spleen cells were mild, the value of SI(Stimulating index) was 1.23±0.15, 1.13±0.16 respectively. The differences between the two groups were not significant (P>0.05). But the response of BALB/c mice spleen cells to Wister rat spleen cells was still violently, the value of SI was 2.40±0.26. And the differences were significant between the front two groups and it separately (P<0.01). The response of normal BALB/c mice only conditioned TBI spleen cells to normal SD rat spleen cells was still violent, the values of SI were 2.16±0.12, and thedifferences were significant between the front two groups and it separately also(P<0.01).4. In this study, we observed mice of group A did not appeared GVHD. But mice of group B four appeared with variant degree of body weight loss,bow postural, wasting, diarrhea, losing of fur, and so on, then all died within 23 days. The slice of liver and intestine displayed pathologic changes. It mainly were that focal necrosis and lymphocyte or inflammatory cells infiltrating and destruction of intestinal mucosa structure. It accorded with GVHD. Mice of group C only one appeared with feebleness GVHD. But we didn't observe chronic GVHD in group A and group C all for 150 days. Surviving time of group B compared with group C was significa...
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