Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The technique using the IBM 2991 blood cell processor is an effective technique for the concentration of mononuclear cells from large volumes of bone marrow. The marrow cells are layered on to Ficoll Metrizoate using the IBM processing set. The mononuclear cells and CFU-GM recoveries are in close relationship with the hematocrit of the cell suspension processed. Twenty two bone marrows have been collected and purified according to this protocol. The mononuclear cell recovery is an average of 78,3% (range: 44-92%) and the CFU-GM recovery is in average of 67,5% (range: 40-89%). At the end of the procedure the cell viability is satisfying (97,1% +/- 1,7 are trypan blue negatives). When it is necessary to remove from the bone marrow collected either malignant cells prior autologous bone marrow graft or T lymphocytes in an attempt to prevent GVHD in allogeneic BMT, the purity of marrow cell suspension become a fundamental parameter.
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PMID:[Method for concentrating marrow stem cells using the IBM 2991 washer. Necessary preparation before in vitro treatment of bone marrow by pharmacologic or immunologic means]. 634 24

We have previously found that a major histocompatibility complex (MHC) restriction exists between pluripotent hemopoietic stem cells (P-HSCs) and stromal cells. Based on this finding, we have recently found using chimerism-resistant mouse combinations that successful allogeneic (allo) BMT can be executed by recruiting donor bone marrow stromal cells. The strategies include donor bone grafts under the skin, injection of whole bone marrow cells (BMCs) including stromal cells via the portal vein (PV), and injection of whole BMCs directly into the bone marrow cavity (intra-bone marrow [IBM] injection). In this paper, we show how stromal cells play crucial roles in overcoming chimerism-resistant allo BMT.
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PMID:Successful allogeneic bone marrow transplantation. Crucial roles of stromal cells in prevention of graft rejection. 1146 92

Using various autoimmune-prone mice, we have previously shown that conventional allo BMT can be used to treat a range of autoimmune diseases. These findings have recently been confirmed even in humans. However, in humans, the success rate of BMT across major histocompatibility complex(MHC) barriers is lowered by graft-versus-host disease(GvHD), graft rejection, and incomplete T-cell recovery. We have just established a new BMT method in which bone marrow cells(BMCs) are directly injected into the intra-bone marrow(IBM-BMT). We here show that 'IBM-BMT' is the best strategy for allo BMT and also organ allografts to induce persistent tolerance.
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PMID:[New strategies for BMT]. 1251 Mar 55

In humans, the success rate of BMT across major histocompatibility complex (MHC) barriers is lowered by graft-versus-host disease (GvHD), graft rejection and incomplete T-cell recovery. To prevent GvHD, we attempted to minimize the contamination of bone marrow cells (BMCs) with T cells from the peripheral blood when donor BMCs were collected, finally establishing a new 'Perfusion Method' using cynomolgus monkeys. There was significantly less contamination of BMCs with T cells in this method (<6%) than in the conventional 'Aspiration Method' (>20%) consisting of multiple aspirations of BMCs from the iliac crest. Using radio-sensitive and chimerism-resistant MRL/lpr mice, we also established a new method for allogeneic (allo) BMT and organ allografts. In this method, whole BMCs, containing a small number of T cells and mesenchymal stem cells (MSCs), were directly injected into the bone marrow cavity (intrabone marrow [IBM]-BMT). MRL/lpr mice treated with IBM-BMT survived more than 2 years without showing the symptoms of autoimmune diseases. IBM-BMT thus has several advantages: (i) no GvHD develops even if T cells are not depleted from BMCs; (ii) no graft failure occurs even if the dose of radiation as the conditioning regimen for allo BMT is reduced to 5Gy x 2; (iii) hemopoietic recovery is rapid; and (iv) the restoration of T-cell functions is quick and complete even in donor-recipient combinations across MHC barriers. We believe that these strategies for allo BMT and organ allografts herald a new era in transplantation, and that they would be helpful in allogeneic HSCT of autoimmune diseases.
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PMID:New strategies for allogeneic BMT. 1293 Dec 48

Donor lymphocyte infusion (DLI) is clinically used for the treatment of malignant tumors. We have found recently that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to treat various autoimmune diseases, even when radiation doses are reduced. In addition, recently we have found that IBM-BMT can prevent not only graft failure but also graft-versus-host disease (GvHD). Based on these findings, we attempted to prevent and treat the progression of a tumor (Meth-A cell line: BALB/c-derived fibrosarcoma) by DLI plus IBM-BMT. When the tumors had grown to approximately 10 x 10 mm, the tumor-bearing BALB/c (H-2(d)) mice were irradiated with 5 Gy, and whole spleen cells from C57BL/6J (B6) (H-2(b)) mice (as DLI) were then intravenously injected into the BALB/c mice. Simultaneously, bone marrow cells (BMCs) from B6 mice were injected directly into the bone marrow cavity of the BALB/c mice (IBM-BMT). The tumors decreased in size, but the mice died of GvHD. However, when CD4(+) T-cell-depleted spleen cells were used for DLI, the recipients showed only mild GvHD and survived longer, due to the slow growth of the tumor. In contrast, when CD8(+) T-cell-depleted spleen cells were used for DLI, the recipients showed more severe GvHD than those injected with whole spleen cells. These results suggest that IBM-BMT plus DLI (the depletion or reduction of a certain cell population like CD4(+) T cells) could be helpful to suppress both GvHD and tumor growth.
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PMID:A new strategy for treatment of malignant tumor: intra-bone marrow-bone marrow transplantation plus CD4- donor lymphocyte infusion. 1574 31

This study was aimed to explore the effects and mechanisms of transplantation tolerance induced by "TBI + cyclophosphamide (CTX)" regimen combined with intra-bone marrow injection of allogenic BMCs. On day 0 C57BL/6 (H-2(b), B6) mice received sublethal dose of total body irradiation (TBI) ((60)Co gamma-ray) followed by intrabone marrow-bone marrow transplantation (IBM-BMT) of 3 x 10(7) cells/30 microl BMCs from BALB/c (H-2(d)) mice. The recipient mice were given CTX intraperitoneally 2 days after IBM-BMT. On day 7 skin grafting was performed and the skin survival was observed. The tolerance mechanism was investigated by mixed lymphocyte reaction (MLR), IL-2 reverse test, adoptive transfer assay in vitro. The results showed that the mean survival time (MST) of skin allografts in group treated with TBI + CTX + BMT was significantly longer, compared with that of other groups (P < 0.01). On day 90 after IBM-BMT, the phenotypic character of the recipient mice (black color) began to convert to that of the donor mice (white color). The MLR demonstrated that the immune responses of recipient mice were donor-specific tolerance. Suppressive activity in the spleen cells of tolerant B6 mice was observed in adoptive transfer assay in vitro. IL-2 reversal and the phenotypic conversion showed that the tolerance mechanisms were involved in clonal anergy and the development of chimerism. It is concluded that the nonmyeloablative regimen combined with IBM-BMT can induce a long-term tolerance, and the multiple mechanisms including clonal anergy, suppressor cells and chimerism were involved in transplantation immune tolerance.
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PMID:[Induction of immune tolerance for allogenic recipient mice by non-myeloablative bone marrow transplantation]. 1640 79

The purpose of hematopoietic stem cell transplantation by intra-bone marrow injection (IBM-HSCT) is to facilitate the homing of HSC. It has been recently proven in many animal experiments that different kinds of donor cells could efficiently home and engraft into the bone marrow by IBM-HSCT, which led to the rapid hemopoietic and immune recovery of recipients, preventing the development of GVHD, inducing the donor-specific tolerance in allogeneic organ transplantation, and promoting the survival rate of recipients. In this review, the effect of IBM-BMT and IBM-UCBT, the application of IBM injection technique in the study on HSC's biological characteristics, and its prospect for clinical HSCT were summarized.
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PMID:[Progress of research and application on hematopoietic stem cell transplantation by intra-bone marrow injection--review]. 1658 20

Using small animals (mice and rats) and monkeys, we have found that the combination of bone marrow collection using the perfusion method (PM) and intra-bone marrow-bone marrow transplantation (IBM-BMT) of the collected cells is safe and effective in treating various intractable diseases. Based on these findings, we attempted to apply this method to humans. We report here the first case of a patient (6 years old) with beta-thalassemia major who underwent allogeneic BMT using this new PM + IBM-BMT method. The white blood cell counts of the patient gradually increased to more than 1500/microL by day 47 and continued to increase, reaching the highest level (8600/microL) on day +55. Fluorescence in situ hybridization data on day +33 showed that 98% of the peripheral blood cells were from the donor. Notably, there were no symptoms of graft-versus-host disease (GvHD). However, on day +56, the patient regrettably died of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy. We hope that this case report will help make our new strategies more readily available for the treatment of patients with various intractable diseases.
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PMID:An innovative approach to bone marrow collection and transplantation in a patient with beta-thalassemia major: marrow collection using a perfusion method followed by intra-bone marrow injection of collected bone marrow cells. 1726 5

We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4(+) cell-depleted spleen cells (CD4(-) cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4(-) cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell-depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4(+) cell-depleted spleen cells (CD4(-) cells) or CD8(+) cell-depleted spleen cells (CD8(-) cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8(-) cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4(-) cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4(-) cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4(-) cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4(-) cells could become a new strategy for the treatment of solid tumors.
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PMID:Allogeneic intrabone marrow-bone marrow transplantation plus donor lymphocyte infusion suppresses growth of colon cancer cells implanted in skin and liver of rats. 1728 50

A P6 substrain of the senescence accelerated mouse (SAMP6) spontaneously develops osteoporosis early in life. These mice show the clinical signs of osteoporosis, such as elevated levels of urinary deoxypyridinoline (Dpd), decreased bone mineral density (BMD), and a significant loss of trabecular and cortical bone thickness at 12 months of age. Here, we describe the transfer of osteoporosis to a normal strain by the injection of bone marrow cells from SAMP6 donors directly into the bone marrow cavity (intra-bone marrow-bone marrow transplantation [IBM-BMT]). More than 1 month after IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells that could differentiate into osteocytes were also found to be of donor origin. In addition, the recipient C57BL/6 mouse showed the features of osteoporosis in the trabecular bone. Decreases in BMD and increases in urinary Dpd were also observed. When the message levels of cytokines (interleukin [IL]-11, IL-6, receptor activator of NF-kappaB ligand [RANKL], osteoprotegerin, macrophage-colony-stimulating factor, and insulin-like growth factor-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis, IL-6 and IL-11 were reduced to a level similar to that in SAMP6 mice, whereas that of RANKL was increased. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment are reconstituted as a result of IBM-BMT, and suggest that the development of senile osteoporosis might be attributable to "stem cell disorders." Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:Induction of senile osteoporosis in normal mice by intra-bone marrow-bone marrow transplantation from osteoporosis-prone mice. 1734 92


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