| Background:Because of the uniquely curable role for many malignant or benign diseases, hematopoietic stem cell transplantation (HSCT) has been widely accepted. Also, it has made great progress due to the deepened understanding of associated factors during HSCT. It is critical for infused stem cells to home to the appropriate microenvironment to set up the new hematopoiesis and immune system. The efforts to increasing engraftment efficiency were not fully emphasized in the clinical situation because the mechanism under engraft was poorly understood. Fortunately, the increased engraftment could be successfully achieved by infusing times of hematopoietic cells from donor. But many negative effects were also noticed when such strategies were adopted. Recently the intra-bone marrow injection was suggested as a transplantation method in HSCT. The higher efficacy of engraftment and less GVHD made it a valuable method which may lead to a more exciting future for HSCT. However there were rare researches to compare the effects that the sources of stem cells and the intensity of conditioning regimen would have on the recovery of donor’s hematopoiesis in IBM-HSCT.Objective:To verify the hypothesis that the graft source and conditioning regimens would change the efficiency of donor’s engraftment and hematopoietic recovery in IBM-HSCT.Method:Mononuclear cells from male C57BL/6(H2b) mice’s bone marrow or mobilized peripheral mononuclear cells were bilaterally intra-bone injected into the Female BALB/c (H-2d) mice which had been conditioned with3Gy or6Gy TBI. In some cases, mobilized bone marrow cells were also used. The total amount of cells for each recipient t were1×106donor cells while the negative controls were treated with pure PBS solution. The survival, general condition, weight, count of peripheral white blood cell, and donor chimerism were regularly evaluated. Scores of histopathological GVHD were recorded in some recipients.Results:1. All mice treated with myeloablative conditioning regimen suffered radiation injury. For mice that were treated with IBM of static BMNCs, the leucocyte counts and weights were significantly correlated with the days after transplant. Leukocytes increased from0at+7d to1.0×109/L between+17d and+19d. Mice continued to gain their weights from14days delay after the transplant. At+30day, good recover of the leukocyte count (3.2±0.7)×109/L and nearly full donor chimerism (96%) were noticed with a100%survival rate. The GVHD pathologic score was3.5±1.2in mice treated with bone marrow grafts. On the contrary, among the mPMNCs-IBM group, only one of them survived after myeloablative conditioning.2. After nonmyeloablative conditioning regimen, all mice in each group were in good condition and had no obvious radiation injury or obvious transplantation-related toxic ity. Their weight-gains were not delayed after transplant. When evaluated at the time point of+30d, the mPMNCs-EBM group had the best leucocyte count (2.45±0.46) x109/L. However, BMCs-IBM group showed the best recovery of leucocyte count (3.70±1.00)×109/L at+60d. The best chimerism rates were recorded at both+30d and+2.5month evaluation (15.7%±6.2%and90.80%±4.42%).3. Mice that were treated with myeloablative conditioning followed by BMNCs-IBM had earlier recovery of leucocyte at+30d than of nonmyeloablative conditioning (3.3×106/L and1.5×106/L, p<0.001). A significant better donor chimerism was also presented in mice treated with myeloablative conditioning.(96%vs16%p<0.001).Conclusions:1. Low dose of BMNCs can successfully engraft either after high-intensity conditioning regimen or reduced-intensity conditioning regimen even no immunosuppression was enforced. 2. In the IBM-HSCT modes,high-intensity conditioning regimen is more effective than RIC in term of engraftment, but with severer radiation injury.3. Under the same low dose level, BMNCs is superior to mPBMNCs in term of donor hematopoietic reconstitution. So BMNCs may be the preferable source of donor stem cells if IBM-HSCT is chosen to deliver the grafts. |
PDF Full Text Request