Successful liver allografts in mice by combination with allogeneic bone marrow transplantation.

Nakamura, Toshio; Good, Robert A.; Yasumizu, Ryoji; Inoue, Shiro; Oo, Maung Maung; Hamashima, Yoshihiro; Ikehara, Susumu

doi:10.1073/pnas.83.12.4529

Cited by 52 publications

(35 citation statements)

References 12 publications

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“…10,11 However, this method was not applicable to humans because of lethal levels of irradiation, and allogeneic BMT in humans has several other problems such as GvHD. As described here, we have recently found that 'PV-BMT' is better than 'IV-BMT'.…”

Section: Discussionmentioning

confidence: 99%

New strategies for allogeneic BMT

Ikehara

2003

Bone Marrow Transplant

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Summary: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 (o6%) than in the conventional 'Aspiration Method' (420%) 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 Â 2; (iii) hemopoietic recovery is rapid; and (iv) the restoration of T-cell functions is quick and complete even in donorrecipient 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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Section: Discussionmentioning

confidence: 99%

New strategies for allogeneic BMT

Ikehara

2003

Bone Marrow Transplant

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“…There have been reports of tolerance against the transplanted liver after OLT in mice [14], primates [21], and humans [12,171. Several studies in humans show enhanced allograft survival [ 19,201 when repeated BM infusions are given after allograft transplantation or at the time of OLT.…”

Section: Discussionmentioning

confidence: 99%

Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance

Stachel

Schmid²,

Lang³

et al. 2002

Transplant Int

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A 2-year-old boy underwent liver transplantation for fulminant hepatic failure of unknown cause. Four months later the child developed severe aplastic anemia. Allogeneic bone marrow transplantation (BMT) was performed using marrow from his 14-month-old HLA-identical sister. Severe aplastic anemia recurred 2.5 months later. After reconditioning a second BMT was performed using the same donor. Tapering of immunosuppression 2 years after BMT led to biopsy-confirmed rejection of the liver. Therapy with high-dose corticosteroids and an increase in cyclosporine A medication readily reversed rejection and a low-dose immunosuppression reflected by cyclosporine trough levels less than 50 ng/ml has been maintained since. Eight years later the boy is in excellent health with both bone marrow and liver functioning perfectly. In summary, this case demonstrates that even recurrent severe aplastic anemia after OLT can be cured by BMT, and that a transplanted liver can tolerate a double conditioning regimen without problems. Tolerance towards the liver through BMT did not develop.

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“…We previously found that the combination of organ allografts and IBM-BMT from the same donors was the most effective strategy to prevent the rejection of organ allografts, since the radiation dose could be reduced to 4Gy x 2 in skin allografts [76,77]. In addition, we have found that IBM-BMT is applicable to allografts of other organs and tissues in rats and mice, such as pancreas islets, legs, lungs, heart and ovary [78][79][80][81][82][83] .…”

Section: Intra Bone Marrow-bmt (Ibm-bmt) For Metabolic Disorders and mentioning

confidence: 99%

Immunomodulatory Properties and Therapeutic Application of Bone Marrow Derived-Mesenchymal Stem Cells

Ikehara²

2013

J Bone Marrow Res

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Mesenchymal stem cells (MSCs) are prototypical adult stem cells, identified as an adherent, fibroblast-like population positive for CD105, CD90 and CD73, and lacking hematopietic markers. MSCs can be isolated from different adult tissues including bone marrow (BM), umbilical cord, skeletal muscle and adipose tissue. MSCs have a potent immunomodulatory function via soluble factors, including PGE2, TGF-β, indoleamine 2,3-dioxygenase (IDO), IL-10, and HGF. Treatment with MSCs can improve type 1 diabetes, liver fibrosis and arthritis via their immunomodulatory function. Intra-bone marrowbone marrow transplantation (IBM-BMT) can replace not only hemopoietic stem cells (HSCs) but also MSCs. IBM-BMT seems to be the best strategy for allogeneic BMT, and may improve aging-related diseases, including type 2 diabetes and osteoporosis. IBM-BMT has also been shown to be the most effective strategy to prevent the rejection of organ allografts. This review summarizes the immunomodulatory properties and therapeutic application of bone marrow derived-MSCs.

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Successful liver allografts in mice by combination with allogeneic bone marrow transplantation.

Abstract: Successful liver allografts were established by combination with allogeneic bone marrow transplantation.

Cited by 52 publications

References 12 publications

New strategies for allogeneic BMT

New strategies for allogeneic BMT

Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance

Immunomodulatory Properties and Therapeutic Application of Bone Marrow Derived-Mesenchymal Stem Cells

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