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Abstract
Using animal models for autoimmune diseases, we have previously shown that allogeneic bone marrow transplantation (allo BMT) can be used to treat autoimmune diseases. Using cynomolgus monkeys, we have recently developed new BMT methods for the treatment of autoimmune diseases. The methods include the perfusion method (PM) for the collection of bone marrow cells (BMCs), and intra-bone marrow (IBM)-BMT for the direct injection of collected whole BMCs into the bone marrow cavity. The PM, in comparison with the conventional aspiration method, can minimize the contamination of BMCs with T cells from the peripheral blood. Therefore, without removing T cells, no graft-versus-host disease (GvHD) develops in the case of the PM. Since BMCs collected by the PM contain not only hemopoietic stem cells (HSCs) but also mesenchymal stem cells (MSCs), the injection of both cells directly into the bone marrow cavity (IBM–BMT) facilitates the engraftment of donor hemopoietic cells. In organ allografts with IBM–BMT, no graft failure occurs even if the radiation dose is reduced. In addition, IBM–BMT is applicable to regeneration therapy and various age-associated diseases such as osteoporosis, since it can efficiently recruit donor-derived normal MSCs.
We have also found that IBM–BMT in conjunction with donor lymphocyte infusion can prevent GvHD, but suppress tumor growth. We believe that this strategy heralds a revolution in the field of transplantation (BMT and organ allografts) and regeneration therapy.
| Abbreviations | ||
| allo BMT | = | allogeneic bone marrow transplantation |
| BMT | = | bone marrow transplantation |
| PM | = | perfusion method |
| IBM | = | intra-bone marrow |
| BMCs | = | bone marrow cells |
| GvHD | = | graft-versus-host disease |
| HSCs | = | hemopoietic stem cells |
| EAE | = | experimental allergic encephalitis |
| MSCs | = | mesenchymal stem cells |
| DLI | = | donor lymphocyte infusion |
| MHC | = | major histocompatibility complex |
| auto BMT | = | autologous BMT |
| PBSCT | = | peripheral blood stem cell transplantation |
| P-HSCs | = | pluripotent hemopoietic stem cells |
| AM | = | aspiration method |
| Abbreviations | ||
| allo BMT | = | allogeneic bone marrow transplantation |
| BMT | = | bone marrow transplantation |
| PM | = | perfusion method |
| IBM | = | intra-bone marrow |
| BMCs | = | bone marrow cells |
| GvHD | = | graft-versus-host disease |
| HSCs | = | hemopoietic stem cells |
| EAE | = | experimental allergic encephalitis |
| MSCs | = | mesenchymal stem cells |
| DLI | = | donor lymphocyte infusion |
| MHC | = | major histocompatibility complex |
| auto BMT | = | autologous BMT |
| PBSCT | = | peripheral blood stem cell transplantation |
| P-HSCs | = | pluripotent hemopoietic stem cells |
| AM | = | aspiration method |
Acknowledgements
The authors thank Mr Hilary Eastwick-Field, Mr Brian O'Flaherty, and Ms K. Ando for their help in the preparation of the manuscript. Supported by a grant from Haiteku Research Center of the Ministry of Education, a grant from the Science Frontier program of the Ministry of Education, Culture, Sports, Science and Technology, a grant from The 21st Century Center of Excellence (COE) program of the Ministry of Education, Culture, Sports, Science and Technology, and also a grant from the Department of Transplantation for Regeneration Therapy (Sponsored by Otsuka Pharmaceutical Company, Ltd), a grant from Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd, and a grant from Japan Immunoresearch Laboratories Co., Ltd (JIMRO).
Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.