Ikehara Susumu
First Department of Pathology, Transplantation Center, Regeneration Research Center for intractable Diseases, Kansai Medical University, Osaka 570-8506, USA.
Hematology. 2003 Apr;8(2):77-81. doi: 10.1080/1024533031000084240.
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.
骨髓移植（BMT）正成为治疗血液系统疾病、先天性免疫缺陷、代谢紊乱以及自身免疫性疾病的有力策略。我们之前使用各种自发性自身免疫性疾病动物模型发现，同种异体骨髓移植（allo BMT）可用于预防和治疗各种自身免疫性疾病。此外，我们还发现自身免疫性疾病是干细胞紊乱性疾病。然而，在对辐射敏感（<8.5 Gy）的MRL/lpr小鼠中，我们发现传统的BMT对自身免疫性疾病仅有短暂疗效，这些疾病会复发。因此，我们专注于探索在辐射敏感且嵌合抗性的MRL/lpr小鼠中预防和治疗自身免疫性疾病的新策略。利用MRL/lpr小鼠，我们建立了一种新的allo BMT方法。在该方法中，将含有少量T细胞和间充质干细胞（MSC）的全骨髓细胞（BMC）直接注入骨髓腔（骨髓内[IBM]-BMT）。接受IBM-BMT治疗的MRL/lpr小鼠存活超过2年，且未出现自身免疫性疾病症状。为了将这种BMT方法应用于人类，我们还利用食蟹猴建立了一种新的BMC采集方法。在该方法中，使用“灌注法”（PM）从长骨采集BMC，然后将整个BMC（包括MSC）直接注入IBM。我们相信，这种新方法将成为治疗各种难治性疾病的有力策略，包括骨质疏松症等与年龄相关的疾病。
