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      New strategies for BMT, organ transplantation, and regeneration therapy.

      Hematology (Amsterdam, Netherlands)

      Transplantation, Homologous, methods, Tissue and Organ Harvesting, transplantation, Stromal Cells, Stem Cell Transplantation, Safety, Regeneration, Radiation Chimera, Portal Vein, prevention & control, genetics, Osteoporosis, Organ Transplantation, Models, Animal, Mice, Inbred MRL lpr, Mice, Macaca fascicularis, therapy, Lupus Erythematosus, Systemic, Injections, Intravenous, Injections, Immune Tolerance, Humans, Graft vs Host Disease, Bone Marrow Transplantation, Bone Marrow, Autoimmune Diseases, Animals

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          Bone marrow transplantation (BMT) is becoming a powerful strategy for the treatment of hematologic disorders, congenital immunodeficiencies, metabolic disorders and also autoimmune diseases. We have previously found using various animal models for spontaneous autoimmune diseases, that allogeneic bone marrow transplantation (allo BMT) can be used to prevent and treat various autoimmune diseases. In addition, we have found that autoimmune diseases are stem cell disorders. However, in MRL/lpr mice, which are radiosensitive (<8.5 Gy), we found that conventional BMT had only a transient effect on autoimmune diseases, which were found to recur. Therefore, we concentrated on discovering new strategies to prevent and treat autoimmune diseases in the radiosensitive and chimeric-resistant MRL/lpr mouse. Using MRL/lpr mice, we established a new method for allo BMT. In this method, whole bone marrow cells (BMCs), containing a small number of T cells and mesenchymal stem cells (MSCs), were directly injected into the bone marrow cavity (intra-bone marrow [IBM]-BMT). MRL/lpr mice treated with IBM-BMT survived more than 2 years without showing the symptoms of autoimmune diseases. To apply this BMT method to humans, we have also established a new method for BMC harvesting using cynomolgus monkeys. In this method, BMCs are harvested from the long bones using a "Perfusion Method" (PM) and the whole BMCs (including MSCs) are then injected directly into the IBM. We believe that this new method will become a powerful strategy for the treatment of various intractable diseases, including age-associated diseases such as osteoporosis.

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