Ikehara Susumu
First Department of Pathology, Transplantation Center, Regeneration Research Center for Intractable Diseases, Center for Cancer Therapy, Kansai Medical University, Moriguchi City, Osaka, Japan.
J Hematother Stem Cell Res. 2003 Dec;12(6):643-53. doi: 10.1089/15258160360732678.
The author previously proposed a new concept of categorizing stem cell disorders as: (1) stem cell aplasia (aplastic anemia), (2) monoclonal hematopoietic stem cell proliferative syndrome (leukemia and myelodysplastic syndrome), and (3) polyclonal hemopoietic stem cell proliferative syndrome (systemic and organ-specific autoimmune diseases). This review includes the following two stem cell disorders: mesenchymal stem cell disorders and organ-specific stem cell disorders. Age-associated diseases such as Alzheimer's disease, osteoporosis, and lung fibrosis belong to the former, whereas carcinosarcoma in the lung and adeno-endocrine cell carcinoma in the stomach belong to the latter. Recently, we have established a new method for allogeneic bone marrow transplantation using chimerism-resistant autoimmune-prone MRL/lpr mice. In this method, whole bone marrow cells containing a small number of T cells and mesenchymal stem cells are directly injected into the bone marrow cavity. MRL/lpr mice treated by injection of stem cells survived more than 2 years without showing symptoms of autoimmune disease. To apply this method to humans, we established a new method for bone marrow cell harvesting using cynomolgus monkeys. In this method, cells are harvested from the long bones using a perfusion method and are then injected directly into the bone marrow cavity of recipients. In this review, we show that this new method may become a powerful strategy for the treatment of various intractable diseases.
作者此前提出了一种将干细胞疾病分类的新概念,即:(1)干细胞发育不全(再生障碍性贫血),(2)单克隆造血干细胞增殖综合征(白血病和骨髓增生异常综合征),以及(3)多克隆造血干细胞增殖综合征(全身性和器官特异性自身免疫性疾病)。本综述涵盖以下两种干细胞疾病:间充质干细胞疾病和器官特异性干细胞疾病。与年龄相关的疾病,如阿尔茨海默病、骨质疏松症和肺纤维化属于前者,而肺肉瘤癌和胃腺内分泌细胞癌属于后者。最近,我们利用抗嵌合自身免疫易感性MRL/lpr小鼠建立了一种同种异体骨髓移植的新方法。在该方法中,将含有少量T细胞和间充质干细胞的全骨髓细胞直接注入骨髓腔。通过注射干细胞治疗的MRL/lpr小鼠存活超过2年,且未表现出自身免疫性疾病的症状。为了将该方法应用于人类,我们利用食蟹猴建立了一种新的骨髓细胞采集方法。在该方法中,使用灌注法从长骨中采集细胞,然后直接注入受体的骨髓腔。在本综述中,我们表明这种新方法可能成为治疗各种难治性疾病的有力策略。