Bone Marrow Transplantation ; Corneal Transplantation ; Heart Transplantation ; Humans ; Kidney Transplantation ; Liver Transplantation ; Lung Transplantation ; Organ Transplantation ; Poisoning ; etiology ; surgery

Cyclosporine A, a fungal metabolite, has been known as a potent immunosuppressant in experimental animals and clinical settings of allotransplantation. It has been responsible for improvements on the success of human kidney, liver, heart, lung, and bone marrow allotransplantation. FK-506, a new antilymphocytic agent, has been reported to be a potent immunosuppressive agent discovered in recent years and now being actively investigated. But there are many questions remaining unanswered about the effective dose and possible side effects of FK-506. So we studied the full thickness skin allotransplantation from BALB/c mouse to C57BL mouse to investigate the survival of allografted skin in a mouse model using the different doses of cyclosporine A and FK-506 and to examine the histological findings at the different period. The results were as follows: 1. The mean survival time (MST) of skin allograft in nontreated control group was 8.6 days. 2. The MST of skin allograft in group 3 treated with cyclosprorine A in 10 mg/kg/day for two weeks was 17.7 days, and that of the group 4 treated with FK-506 in 0.5mg/kg/day for two weeks was 19.7 days. The MST of group 4 was longer than that of group 3 (p>0.05). 3. The MST was increased from 19.7 to 23.1 days as the dose of FK-506 increased from 0.5 mg/kg/day to 1 mg/kg/day (p>0.05). 4. There was no difference in MST between long-term(16 weeks) treatment groups of cyclosporine A and FK-506, and the expire rates of the experimental animals were similarly high in both groups (40%, 50%). 5. The combined treatment of low dose cyclosporine A and FK-506 was more effective method to lengthen the MST and to reduce the expire rate than individual high dose treatment of Cs A or FK-506. 6. The expire rates of experimental animal were higher in long-term treatment groups (36.6%) than in short-term treatment groups(7.5%), and the expire rate of combined treatment groups was lowest (20%) among those of long-term treatment groups. The cause of death was not exactly known, but it could be assumed that the toxicity of drugs may result in death. 7. The histologic findings showed necrosis and mononuclear cell infiltration in rejection period that was consistent with the gross findings, but treated groups maintained normal histological architecture a much longer period than the nontreated group. There was no difference in histologic findings between the cyclosporine A treated groups and FK-506 treated groups. With the above results, it can be concluded that FK-506 and Cs A prolonged the survival of skin allotransplantation in mouse. and the low-dose combined treatment of these two drugs is the most effective method for reducing the rejection. It can be expected that adequate use of these immunosuppressants may be useful for skin allografting in severed burn patients and composite tissue transplantation.
Allografts* ; Animals ; Bone Marrow ; Burns ; Cause of Death ; Cyclosporine* ; Heart ; Humans ; Immunosuppressive Agents ; Kidney ; Liver ; Lung ; Mice* ; Mice, Inbred C57BL ; Necrosis ; Skin* ; Survival Rate ; Tacrolimus* ; Tissue Transplantation ; Transplantation, Homologous ; Transplants

BACKGROUND: Human bone marrow contains mesenchymal stem cells (MSCs) which are capable of differentiation into a number of mesenchymal cell lineages when stimulated under appropriate conditions. Many studies indicate that the bone marrow stroma is damaged following bone marrow transplantation. Animal models suggest that the transplantation of healthy stromal elements, including MSCs, may enhance the ability of the bone marrow microenvironment to support hematopoiesis after stem cell transplantation. However, it remains to be seen whether transplantation of MSCs has significant value and pre-culture of hematopoietic stem cells with MSCs prior to transplantation changes their engraftment. METHODS: We investigated the differentiation potential and the potential plasticity of MSCs. And we also studied whether they have any effects on hematopoietic engraftment in xenotransplantation animal model. RESULTS: Culture-expanded human MSCs exhibited a spindle-shaped fibroblastic morphology and were differentiated into adipocytes, osteoblasts, and chondrocytes in specific culture conditions. In xenograft animal model, human ex vivo expanded marrow-derived MSCs were cotransplantated with human CD34+ cells into NOD/SCID mice and demonstrated about a two-fold increase in bone marrow engraftment as determined by human CD45+ and CD34+ expression as compared to transplantation of CD34+ cells alone. Also MSCs resulted in a two-fold to three-fold increase in bone marrow engraftment of CD45+- CD33+ cells and CD45+- CD13+ cells, whereas no such effect were observed in engraftment of CD45+- CD3+ cells and CD45+- CD19+ cells. To determine the homing and engraftment of MSCs, we performed cotransplantation of human CD34+ cells with ex vivo expanded human MSCs that had been retrovirally transduced with GFP transgene into NOD/SCID mice. Expression of GFP was found in the bone marrow of 1 of 5 NOD/SCID mice by DNA-PCR analysis. Using DNA-PCR, we found human beta2-microglobulin expression in liver, spleen, thymus, lung, heart, kidney, and small intestine. CONCLUSION: These results suggest that MSCs are capable of enhancing hematopoietic engraftment and they also may possess therapeutic value for the repair of damaged mesenchymal tissues following hematopoietic stem cell transplantation.
Adipocytes ; Animals ; Bone Marrow ; Bone Marrow Transplantation ; Cell Lineage ; Chondrocytes ; Fibroblasts ; Heart ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Heterografts ; Humans ; Intestine, Small ; Kidney ; Liver ; Lung ; Mesenchymal Stromal Cells* ; Mice ; Models, Animal ; Osteoblasts ; Plastics ; Spleen ; Stem Cell Transplantation ; Thymus Gland ; Transgenes ; Transplantation, Heterologous ; Zidovudine

OBJECTIVETo explore the feasibility and efficiency of lung transplantation in the treatment of bronchiolitis obliterans (BO) after allogeneic bone marrow transplantation (allo-BMT).

METHODSWe reported one case of bilateral lung transplantation for BO after allo-BMT and reviewed the related literatures.

RESULTSA 23 year-old man diagnosed as BO after allo-BMT underwent a sequential bilateral lung transplantation through bilateral anterolateral thoracotomy without sternal division. The patient suffered from acute rejection on post-operation day (POD) 2, and cured by mechanical ventilation, large dose of methylprednisolone and gamma globulin. The patient was transferred out of the intensive care unit on POD 14 and discharged from the hospital on POD 43. Chest CT scans and pulmonary function tests showed good performance in 3 and 6 months follow-up period.

CONCLUSIONBO is one of the late common non-infectious pulmonary complication after allo-BMT. For patients who have no response to medication, lung transplantation is the only efficient treatment choice so far, which can prolong survival and improve the quality of life. However, limited by small samples, optimal surgery time and appropriate care of postoperative complications still need accumulation of experience by multicenter and large samples studies.

Bone Marrow Transplantation ; adverse effects ; Bronchiolitis Obliterans ; etiology ; surgery ; Humans ; Lung Transplantation ; methods ; Male ; Transplantation, Homologous ; Young Adult

The study was aimed to explore the distribution and interaction mechanism of human bone marrow mesenchymal stem cells (MSC) and cord blood cytokine-induced killer (CIK)/natural killer (NK) cells infused via different ways at different times in NOD/SCID mice. 5 microl 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine perchlorate (DiI) dye(red) was added in suspension of MSC per ml, and 1 microl carboxyfluorescein diacetate, succinimidyl ester(CFDA SE) dye(green) was added in suspension of CIK/NK cells per ml. The amounts of MSC and CIK/NK cells infused in each 6 NOD/SCID mouse were 1 x 10(6) (0.1 ml) and 1 x 10(7) (0.1 ml) respectively. All mice were divided into 4 groups, each group consisted of 6 mice. Group A: MSC (intravenous infusion, iv) + CIK/NK cells (iv) at the same time, group B: MSC (iv) + CIK/NK cells (iv) at 48 hours after infusion of MSC; group C: MSC (intramedullary infusion, im) + CIK/NK cells (iv) at the same time; group D: MSC (im) + CIK/NK cells (iv) at 48 hours after infusion of MSC. 3 NOD/SCID mice were sacrificed per batch at 24 hours and 48 hours after infused CIK/NK cells. Frozen sections of liver, spleen, lung and kidney were prepared, and then followed by counting the amounts of red and green fluorescence cells under fluorescence microscope, and calculating the ratio of MSC to CIK/NK cells for reflecting the interaction of MSC and CIK/NK cells in mice, and for showing the suppressive intensity of MSCs on CIK/NK cells. The results showed that the sums of average ratios of MSC to CIK/NK cells in lung, liver and spleen of group A and B were higher than that in group C and D at 24 hours and 48 hours respectively after infusing CIK/NK cells. The sum of average ratios of MSC to CIK/NK cells in group A was slightly higher than that in group B at 24 hours and 48 hours after infusing CIK/NK cells, but there was no significant difference between them. The sum of average ratios of MSC to CIK/NK cells in lung, liver and spleen in group C was slightly lower than that in group D at 24 hours after infusing CIK/NK cells, but reversed at 48 hours later and there was no significant difference between them. The sums of average ratios of MSC to CIK/NK cells in lung, liver and spleen in group A, B, C and D were all higher than those in kidney at 24 and 48 hours respectively after infusing CIK/NK cells. It is concluded, the MSC and CIK/NK cells may interact if they are infused via the same way and at the same time, the location where the suppression of MSC on CIK/NK cells occur in vivo may be reticulo-endothelial systems in lungs and livers.
Animals ; Bone Marrow Transplantation ; Cell Communication ; Cytokine-Induced Killer Cells ; transplantation ; Fetal Blood ; cytology ; Humans ; Killer Cells, Natural ; transplantation ; Liver ; cytology ; Lung ; cytology ; Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Transplantation, Heterologous

OBJECTIVETo investigate the variations type of hepatic artery and discuss the method of how to protect hepatic artery from injury during the quick harvest of the donor liver.

METHODSA retrospective review of the variations of hepatic arteries of the donor livers and the course of excision and reconstruction of 200 donor livers was performed, and the aberrance and reconstruction method of hepatic arteries were summarized.

RESULTS37 out of 200 hepatic arteries varied and 2 patients suffered biliary complications because of improper preservation of aberrant hepatic arteries.

CONCLUSIONSMost aberrant liver arteries come from superior mesenteric artery or left gastric artery. Proper quick harvest of multiple organs is the basis of the integrity of hepatic arteries, and all the aberrance must be reconstructed.

Female ; Hepatic Artery ; anatomy & histology ; surgery ; Humans ; Kidney Transplantation ; Liver Transplantation ; methods ; Male ; Retrospective Studies ; Tissue and Organ Harvesting ; methods ; Transplantation, Homologous

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy of high-dose chemotherapy with busulfan, thiotepa and melphalan (BTM) as a myeloablative regimen in allogeneic bone marrow transplantation (allo-BMT) for patients with acute myelogenous leukemia (AML). METHODS: Twenty-seven patients with AML were enrolled; Sixteen patients had standard risk (SR) diseases (first complete remission (CR1) and de novo AML) and eleven patients had high risk (HR) diseases (second, or subsequent remission, secondary AML, relapsed, or refractory AML, CR marrow with persisting extramedullary manifestation (chloroma), or hypoplastic acute leukemia). The conditioning regimen included busulfan 4 mg/kg/day for a total dose of 12 mg/kg; thiotepa 250 mg/m2/day for a total dose of 500 mg/m2; and melphalan 50 mg/m2/day for a total dose of 100 mg/m2. Cyclosporine A and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. RESULTS: The median time to recovery a granulocyte count of 0.5 x 109/L was 14 days (range 10~25 days) and platelet transfusion independence was 30 days (range 12~49 days). The major regimen-related toxicities were gastrointestinal-related symptoms including oral mucositis, nausea, vomiting, and diarrhea. All patients experienced oral mucositis (> or = grade 1) and the patients with oral mucositis of equal and greater than grade 3 were 44% in SR and 45% in HR. The toxicities associated with lung, skin, heart and brain were minimal. Three (11%) patients had severe or fatal veno-occlusive disease (VOD). There were five treatment-related death (19%) (hepatic VOD with multiorgan failure (n=3), pneumonia and ARDS (n=2)) within the first 100 days after allo-BMT. There was not a significant difference between SR and HR group (p=0.167). The incidence of acute GVHD equal or greater than grade II was less than 10%. The actual survival at 2 year was 70.4%(95% confidence interval (CI), 54.7%~86.1%)(SR; 81.3% (95% CI; 63.4~99.1%) vs HR; 54.6% (95% CI; 28.7~80.4%), p=0.154). After a median follow-up of 630 days, 18 of 27 (67%, 355~1062 days) patients are alive without evidence of disease. Three of the 27 patients relapsed (SR; 0% vs HR; 55.6% (95% CI; 19.6~71.3%), p=0.004). CONCLUSION: The BTM regimen followed by allo-BMT is associated with acceptable toxicity and appears to have significant activity in patients with AML. It should be used with caution in patients with prior hepatopathy or refractory state who have an increased risk of severe VOD. Busulfan, thiotepa, and melphalan is an effective and alternative myeloablative regimen for patients with AML.
Bone Marrow Transplantation* ; Bone Marrow* ; Brain ; Busulfan* ; Cyclosporine ; Diarrhea ; Drug Therapy ; Follow-Up Studies ; Graft vs Host Disease ; Granulocytes ; Heart ; Humans ; Incidence ; Leukemia, Myeloid, Acute* ; Lung ; Melphalan* ; Methotrexate ; Nausea ; Platelet Transfusion ; Pneumonia ; Skin ; Stomatitis ; Thiotepa* ; Transplantation, Homologous ; Vomiting

The objective of this study was to investigate the curative effect of combined sibling umbilical cord blood and bone marrow transplantation in treatment of beta-thalassemia major. Combined umbilical cord blood and bone marrow transplantation from an HLA-identical sibling were performed for 3 patients with beta-thalassemia major. The nucleated cells infused into 3 recipients were 19.5 x 10(7)/kg, 20.8 x 10(7)/kg and 23.3 x 10(7)/kg respectively. They accepted the conditioning regimen consisting of busulfan, cyclophosphamide, antithymocyteglobulin. The results showed that three patients gained protracted and stable engraftment. The time to achieve more than 0.5 x 10(9)/L neutrophils in three patients was 16, 18, and 17 days respectively; the time to achieve more than 50 x 10(9)/L platelet in three patients was 48, 50, and 49 days respectively. The speed of hematopoietic recovery was faster than that of umbilical cord blood transplantation (UCBT) only. Three patients all suffered from acute graft-versus-host disease (aGVHD) of I grade. They had lived with free-thalassemia for 1.5, 2.0 and 2.1 years respectively. Their Hb had been maintained at normal level without transfusion. It is concluded that combined UCBT and BMT may be an effective and safe way to treat pediatric beta-thalassemia major.
Blood Donors ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Combined Modality Therapy ; Cord Blood Stem Cell Transplantation ; methods ; Female ; Graft vs Host Disease ; immunology ; prevention & control ; Humans ; Siblings ; Transplantation, Homologous ; Treatment Outcome ; beta-Thalassemia ; therapy

PURPOSE: Peripheral blood stem cells (PBSC) can be mobilized by use of G-CSF alone from normal bone marrow. In this study, feasibility of mobilization, collection, and hematologic recovery after transplantion were evaluated. METHPDS: From normal undamaged bone marrow of normal PBSC donors and patients with high risk brain tumor who had no experience of chemotherapy or radiotherapy, PBSC was mobilized by use of G-CSF alone. Ten ug/kg/day of G-CSF was injected subcutaneously and leukaphereses were done on the fourth and fifth day of G-CSF injection. Nucleated cells (NC), mononuclear cells (MNC), CD34+ cells and colony forming cells (CFC) were counted. Hematologic recovery was evaluated in 4 autologous transplantations and 6 allogeneic transplantations, 4 of which were done after T cell depletion. RESULTS: Twenty four leukaphereses were done in 6 normal donors and 6 patients with high risk brain tumor. Median 603.3 (342.6~834.5) mL/kg of blood was processed for median 447 (392~549) minutes. Collected cells were as follows; NC: 11.88 (3.11~25.89)x108/kg of donor, MNC: 8.66 (2.61~12.84)x10(8)/kg of donor, CD34+ cells: 7.05 (2.95~11.73)x10(6)/kg of donor, CFC: 25.38 (3.62~35.27)x10(5)/kg of donor, respectively. In allogeneic transplantation, time to reach absolute neutrophil count (ANC)> 500/uL, 1,000/ uL and platelet count> 20,000/uL, 50,000/uL were 10 (9~15) days, 11 (9~16) days, 11 (8~30) days, and 32 (19~156) days, respectively. In autologous transplantation, time to reach ANC> 500/uL, 1,000/uL and platelet count> 20,000/uL, 50,000/uL were 9.5 (9~11) days, 10.0 (9~11) days, 10.5 (9~13) days, and 14.5 (13~17) days, respectively. CONCLUSION: Sufficient number of undamaged PBSC was collected from normal bone marrow by use of G-CSF alone. Hematologic recovery after transplantaion was more rapid than allogeneic bone marrow transplantation or autologous PBSCT which was done with cells collected after chemotherapy and/or radiotherapy.
Autografts ; Blood Platelets ; Bone Marrow Transplantation ; Bone Marrow* ; Brain Neoplasms ; Drug Therapy ; Feasibility Studies ; Granulocyte Colony-Stimulating Factor* ; Humans ; Leukapheresis ; Neutrophils ; Peripheral Blood Stem Cell Transplantation ; Radiotherapy ; Stem Cells* ; Tissue Donors ; Transplantation, Autologous ; Transplantation, Homologous

The infusion and persistence in a transplant recipient of donor-derived bone marrow cells (DBMC) of multi-lineage can lead to a state of permanent chimerism. In solid vascular organ transplantation, the donor bone marrow lineage cells can even be derived from the transplant organ, and these cells can be detected in very small numbers in the recipient. This has been called microchimerism. Much controversy has developed with respect to the function of chimeric cells in organ transplantation. One idea is that the occurrence of these donor cells found in microchimerism in the recipient are coincidental and have no long-term beneficial effect on engraftment. A second and opposing view, is that these donor cells have immunoregulatory function that affect both the acute and chronic phases of the recipient anti-donor responses. It follows that detecting quantitative changes in chimerism might serve as an indication of the donor-specific alloimmune or regulatory response that could occur in concert with or independent of other adaptive immune responses. The latter, including autoimmune native disease, need to be controlled in the transplant organ. The safety and immune tolerance potential of DBMC infusion with deceased and living donor renal transplants was evaluated in a non-randomized trial at this center and compared with non-infused controls given identical immunosuppression. Overall DBMC infusions were well tolerated by the recipients. There were no complications from the infusion (s), no episodes of graft-vs-host disease (GVHD) and no increase infections or other complications. In the deceased DBMC- kidney trial, actuarial graft survival at 5 years was superior especially when graft survival was censored for recipient death. Acute rejections were significant reduced in patients given two DBMC infusions, and chronic rejection was dramatically reduced in all DBMC treated patients. The most interesting finding was that the degree of microchimerism slowly increased over the years the DBMC group that had exhibited no rejection episodes. In the DBMC-living related trial, the incidence of acute rejection did not differ between groups. However, DBMC chimerism in recipient iliac crest marrow had increased more rapidly than might be predicted from results previously seen in the cadaver group, despite four times fewer DBMC infused, with the generation of T- regulartory cells in-vitro assays.
*Bone Marrow Transplantation ; Humans ; *Kidney Transplantation ; *Living Donors ; *Tissue Donors ; *Transplantation Chimera ; *Transplantation Tolerance