Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We have recently found that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to prevent graft-versus-host disease (GvHD), even when intensive donor lymphocyte infusion (DLI) is carried out. In the present study, in conjunction with IBM-BMT, allogeneic splenic T cells as DLI were also injected into the bone marrow cavity of lethally irradiated (8.5 Gy) recipients. The extent of GvHD was compared with that of recipients that had received allogeneic IBM-BMT plus i.v. injection of allogeneic T cells (intravenous DLI [IV-DLI]). GvHD in recipients treated with allogeneic IBM-BMT plus IBM-DLI was far milder than in those treated with allogeneic IBM-BMT plus IV-DLI. This was confirmed macroscopically and histopathologically. The frequency of regulatory T cells (Tregs) detected as CD4(+)CD25(+) and CD4(+)Foxp3(+) cells was significantly higher in recipients treated with IBM-BMT plus IBM-DLI than in those treated with IBM-BMT plus IV-DLI. Donor-derived helper T (Th) cells polarized to Th2 type in recipients treated with IBM-BMT plus IBM-DLI, whereas Th1 cells were dominant in recipients treated with IBM-BMT plus IV-DLI. Furthermore, the production of transforming growth factor-beta and hepatocyte growth factor from bone marrow stromal cells was enhanced after IBM-DLI. Thus, IBM-BMT plus IBM-DLI seem to preferentially induce Tregs and Th2, resulting in the prevention of GvHD. Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:Prevention of graft-versus-host disease by intra-bone marrow injection of donor T cells. 1744 64

We have previously shown that the combination of allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells is effective in suppressing tumor growth, but that this does not induce graft-versus-host disease (GVHD) in mice. In this report, we show that formalin-fixed tumor cell-pulsed dendritic cells (FFTCP DCs) have an additive effect with IBM-BMT plus DLI on the suppression of tumor growth, but that the DCs do not augment GVHD. BALB/c mice, which had been subcutaneously inoculated with Meth A (BALB/c-derived fibrosarcoma), were irradiated at a low dose (5 Gy) and were transplanted with bone marrow cells (BMCs) from C57BL/6 (B6) mice into the bone marrow cavity (IBM-BMT). Simultaneously, the mice were intravenously injected with spleen cells from B6 mice, and subcutaneously injected with FFTCP DCs derived from the bone marrow (BM) of B6 mice. At the point of the induction of DCs from BMCs, formalin-fixed Meth A cells were added into the culture. The mice treated with the combination of FFTCP DCs, IBM-BMT and DLI using CD4+ cell-depleted spleen cells showed smaller tumor sizes and longer survival than the mice treated with IBM-BMT plus FFTCP DCs or IBM-BMT plus DLI using CD4+ cell-depleted spleen cells. These results suggest that the combination of FFTCP DCs, IBM-BMT plus DLI using CD4+ cell-depleted spleen cells has potent anti-tumor effects without showing GVHD.
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PMID:Immunotherapy for malignant tumors using combination of allogeneic intra-bone marrow-bone marrow transplantation, donor lymphocyte infusion and dendritic cells. 1748 50

Curative therapy for diabetes mellitus mainly involves pancreas or islet transplantation to recruit insulin-producing cells. This approach is limited, however, because of both the shortage of donor organs and allograft rejection. Intra-bone marrow bone marrow transplantation (IBM-BMT) has recently been shown to be effective in inducing donor-specific tolerance in mice and rats without the use of immunosuppressants. After induction of diabetes in 15 C3H mice with streptozotocin, the mice received both allotransplants of bone marrow cells from C57BL/6 mice by IBM-BMT and injections via the portal vein of insulin-producing cells that were induced in vitro from stem cells derived from adult C57BL/6 bone marrow. We evaluated the expression of these cells by examining the expression of not only insulin but also the crucial transcription factors insulin I and insulin II. The diabetic mice were treated with IBM-BMT and precultured insulin-producing cells. Hyperglycemia was normalized by 5 days after the treatment and remained normal for more than 45 days. This strategy might be applicable to patients with type I diabetes mellitus.
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PMID:Treatment of streptozotocin-induced diabetes mellitus in mice by intra-bone marrow bone marrow transplantation plus portal vein injection of beta cells induced from bone marrow cells. 1819 13

Increase in endothelial cell sloughing and diminished function of endothelial stem cell progenitors in diabetic subjects are well known phenomena. We hypothesized that transplantation of bone marrow stem cells (BMSCs) including mesenchymal stem cells but not limited to CD34(+) stem cells into type 2 diabetic ob mice would restore insulin sensitivity and glucose tolerance. This approach, when combined with induction of HO-1 (a cytoprotective antioxidant system) in the recipient, would further improve bone marrow function. Sublethally irradiated ob mice received BMSC or CD34(+) stem cells from B129SF2/J mice (genetically related) via i.v. or intra bone marrow-bone marrow transplantation (IBM-BMT) at a dose of 5 x 10(6) cells. CD34(+) i.v. administration to ob mice modestly improved glucose tolerance, whereas BMSC administered by the IBM-BMT significantly increased BMSC function, serum adiponectin and glucose tolerance. Induction of HO-1 in the recipients greatly enhanced the ability of BMSC to prevent diabetes. These findings suggest that transplantation of BMSC-mesenchymal stem cells via IBM-BMT in conjunction with induction of HO-1 can eradicate type 2 diabetes. The beneficial effect of HO-1 induction further suggests that the abnormality in endothelial progenitor cells is due to mesenchymal stem cell-stromal cell disorder exacerbated by oxidative stress and decreases in adiponectin. Thus, transplantation of BMSC using the IBM-BMT strategy in conjunction with HO-1 induction offers a novel approach for the treatment of type 2 diabetes.
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PMID:Bone marrow stem cell transplant into intra-bone cavity prevents type 2 diabetes: role of heme oxygenase-adiponectin. 1824 59

We have previously proposed that autoimmune diseases are hemopoietic stem cell (HSC) disorders. In this review article, we provide evidence that most age-associated diseases such as osteoporosis are mesenchymal stem cell (MSC) disorders and, based on this evidence, we propose a new concept of "stem cell disorders (SCDs)", including HSC and MSC disorders. To treat SCDs, we have recently developed a new strategy (intra-bone marrow-bone marrow transplantation: IBM-BMT) for replacing the abnormal stem cells of recipients with donor-derived normal stem cells (both HSCs and MSCs). We here show that this strategy not only can be used to treat SCDs but is also applicable to organ transplantation, since IBM-BMT can induce tolerance (full chimerism) without the need for immunosuppressants even when radiation doses as the conditioning regimen of BMT are reduced to less than 5.0 Gy x 2, which is equivalent to one shot of 8 Gy (a sublethal dose). We believe that this strategy heralds a revolution in the field of transplantation (BMT and organ transplantation) and regeneration therapy.
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PMID:A novel method of bone marrow transplantation (BMT) for intractable autoimmune diseases. 1824 91

We have recently established a novel method for bone marrow transplantation: intra-bone marrow-bone marrow transplantation (IBM-BMT), by which the rapid recovery of donor-derived hematopoiesis can be expected even when reduced radiation doses are used. In this paper, we examine, using mice, whether the combination of pretreatment of recipients with granulocyte-colony-stimulating factor (G-CSF) and IBM-BMT can induce a more rapid recovery of donor-derived hematopoiesis than IBM-BMT alone. We first pretreated recipients with recombinant human (rh) G-CSF (250 microg/kg/day) for 5 consecutive days (days -6 to -2). On day -1, the recipients were irradiated, and IBM-BMT was carried out on day 0. On day 12, we performed colony-forming units of spleen (CFU-S) assays. The combination of G-CSF pretreatment and IBM-BMT augmented the CFU-S counts, the weight of spleens, and the numbers of donor-derived hematopoietic cells. We next analyzed the mechanisms underlying these effects of G-CSF and found that (i) G-CSF induces Th2 polarization, which can prevent graft rejection, and (ii) G-CSF augments natural suppressor activity, which suppresses graft rejection. The combination of G-CSF pretreatment and IBM-BMT can produce the rapid recovery of donor-derived hematopoiesis and suppress graft rejection. This method would lighten the burden on patients in allogeneic BMT.
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PMID:Administration of granulocyte colony-stimulating factor to recipients followed by intra-bone marrow-bone marrow transplantation accelerates acceptance of allogeneic bone marrow cells in mice. 1847 51

We have previously shown that T cells can acquire donor-type major histocompatibility complex (MHC) restriction and can interact with both donor-type antigen-presenting cells (APCs) and B cells, when adult donor bones are co-grafted with intravenous (IV) injection of bone marrow cells (BMCs) in order to supply donor bone marrow (BM) stromal cells. We have also found that the direct injection of donor BMCs into recipient BM (intra-bone marrow-bone marrow transplantation: IBM-BMT) produces more rapid reconstitution (including T-cell functions) and higher survival rates than IV injection (IV-BMT) even in chimerism-resistant combinations. In the present study, we show that the co-administration of bones from suckling (2-3 days old) donor mice is also effective in the IBM-BMT system. Even when a relatively low number of BMCs were injected into adult (more than 15 weeks old) mice, complete reconstitution was achieved in the mice that had received IBM-BMT+bone grafts, but not in the mice that had received IBM-BMT alone. Most BM and splenic adherent cells obtained from the recipients that had received IBM-BMT+bone grafts were reconstituted by donor-type cells. Both T-cell proliferation and plaque-forming cell assays indicated that the T cells of such mice showed donor-type MHC restriction. Moreover, the analyses of thymic sections using confocal microscopy revealed that donor BM stromal cells had migrated into the thymus. Thus, the co-administration of donor bones has great advantages for allogeneic BMT in adult mice.
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PMID:Facilitation of hematopoietic recovery by bone grafts with intra-bone marrow-bone marrow transplantation. 1851 48

Previously, we have shown that liver allografts obtained from the fetus or young mice are accepted when bone marrow cells (BMCs) from adult mice of the same strain are co-grafted. However, for practical clinical use, it is more convenient to obtain both BMCs and liver from the same adult donors. C57BL/6 mice were irradiated with a single high-dose irradiation or two low-dose irradiations and injected with donor BALB/c (8 weeks old) BMCs intravenously (IV-BMT) or directly into the recipient BM cavity (IBM-BMT). Liver tissues taken from the same donor were, on the same day, engrafted under the kidney capsules. Higher survival rates and more complete reconstitution of donor cells were achieved in the IBM-BMT group than in the IV-BMT group, and this was the case in both irradiation protocols. The acceptance of donor liver tissue was seen in all mice in which hematolymphoid cells were replaced by donor-type cells. The liver grafts of the reconstituted mice showed normal morphology and stained positively with anti-albumin antibody and Periodic Acid Schiff (PAs) staining, indicating that the grafted livers were accepted, had grown, and were functioning. These results demonstrate that the acceptance of allogeneic liver can be achieved by cografting donor BMCs via the IBM route.
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PMID:Successful acceptance of adult liver allografts by intra-bone marrow-bone marrow transplantation. 1853 62

We examined the effects of intra-BM-BMT (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor after 5.5 Gy sublethal irradiation (SubLI) or low-dose (3 x 10(6)) BM cell injection (LDBMCI). With SubLI, BALB/c mice that had received 1 x 10(7) bone marrow cells by IBM-BMT plus ATT from B6 mice showed 73% donor chimerism, whereas those treated with IBM-BMT alone showed 45% chimerism. In the LDBMCI with 7Gy irradiation, IBM-BMT plus ATT resulted in a 90% survival rate with 90% chimerism, whereas IBM-BMT alone resulted in a 55% survival rate with 44% chimerism. Although the number of CD4 T cells was higher in IBM-BMT plus ATT than in IBM-BMT alone, the percentages of FoxP3+/CD4+ T cells and lymphocyte functions in the former were almost identical to those in the latter. When treated with IBM-BMT plus donor lymphocyte infusion (DLI), the mice showed a reduced survival time as a result of GVHD, with low numbers of FoxP3+CD4 T cells under either condition, although 100% chimerism was induced. These results suggest that IBM-BMT plus ATT is effective in reconstituting the recipients with donor-derived cells even after SubLI or LDBMCI.
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PMID:Allogeneic intra-BM-BMT plus adult thymus transplantation from same donor has benefits for long-term survival even after sublethal irradiation or low-dose BM cell injection. 1907 14

We have previously found that conventional allogeneic bone marrow transplantation (allo BMT) can be used to treat various spontaneously developed autoimmune diseases in mice. In addition, we have found that autoimmune diseases can be transferred into the normal mice by conventional BMT from autoimmune-prone mice. Based on these findings, we have proposed that autoimmune diseases are "stem cell disorders." To apply allo BMT to humans, we extensively carried out BMT to clarify which cells are essential for successful BMT, and finally found that three types of cells are essential for successful allogeneic BMT: (1) hemopoietic stem cells (HSCs), (2) natural suppressor cells, and (3) stromal cells (including mesenchymal stem cells, MSCs). We have very recently found that MSCs play a crucial role in preventing graft failure, since there is a major histocompatibility complex restriction between HSCs and MSCs. To recruit donor-derived MSCs, we have found that the injection of whole bone marrow cells into the bone marrow cavity (intra-bone marrow-BMT, IBM-BMT) is the best strategy for the treatment of various otherwise intractable diseases, including autoimmune diseases. In this review article, we provide evidence that IBM-BMT heralds a revolution in the field of transplantation and regeneration medicine.
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PMID:The future of stem cell transplantation in autoimmune disease. 1960 32


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