Ikehara Susumu
First Department of Pathology, Transplantation Center, Regeneration Research Center for Intractable Diseases, Center for Cancer Therapy, Kansai Medical University, Moriguchi City, Osaka 570-8506, Japan.
J Autoimmun. 2008 May;30(3):108-15. doi: 10.1016/j.jaut.2007.12.011. Epub 2008 Jan 31.
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.
我们之前曾提出自身免疫性疾病是造血干细胞（HSC）紊乱。在这篇综述文章中，我们提供证据表明，大多数与年龄相关的疾病，如骨质疏松症，是间充质干细胞（MSC）紊乱，基于这一证据，我们提出了“干细胞紊乱（SCDs）”这一新概念，包括HSC和MSC紊乱。为了治疗SCDs，我们最近开发了一种新策略（骨髓内骨髓移植：IBM - BMT），用供体来源的正常干细胞（HSC和MSC）替代受体的异常干细胞。我们在此表明，这种策略不仅可用于治疗SCDs，还适用于器官移植，因为即使将作为骨髓移植预处理方案的辐射剂量降低至小于5.0 Gy×2（相当于单次8 Gy的亚致死剂量），IBM - BMT也能在无需免疫抑制剂的情况下诱导耐受（完全嵌合）。我们相信，这一策略预示着移植领域（骨髓移植和器官移植）及再生治疗的一场革命。
