Establishment of new hematopoietic stem cell transplantation strategy with purified blood CD34+ cells

这项研究的目的是建立一种新的治疗策略，在各种疾病的治疗中，可以在自体和异体环境中使用纯化的血液CD34+细胞进行造血干细胞移植。在自体环境中，不需要的细胞，如淋巴细胞或肿瘤细胞，应通过纯化程序清除。另一方面，在同种异体环境下，对于来自不相合的供者的移植，纯化的主要目的将是有效预防移植物抗宿主病。在研究期间，这些项目被分为三个步骤：1)建立动员和采集程序，2)作为一种新的策略应用于临床，3)对移植后的长期造血和免疫恢复和维持进行评估。第一年，我们比较了血液CD34+…的动员和采集效果儿童和成人捐献者之间有更多的细胞。因此，我们得出结论，儿童可以成为更适合于外周血干细胞捐献的捐赠者，因为注射G-CSF的不良反应较少，动员和采集程序更有效。第二年，我们成功地治疗了一名慢性炎症性关节炎患者，他严重依赖皮质类固醇，导致身材矮小，并遭受心理问题。在这种自体移植中，我们证实了大剂量环磷酰胺和抗淋巴细胞球蛋白联合纯化的血液CD34+细胞的免疫抑制治疗是有效的，并持续了两年以上。从患者和供者的角度来看，移植细胞的功能也是令人满意的。从这些数据中，我们得出结论，部分纯化的血液CD34+细胞是一种有用的干细胞来源，无论是在自体还是在异体环境下的移植。这种类型的移植应该扩展到细胞治疗的新领域。较少

The purpose of this study was the establishment for a new therapeutic strategy in the treatment of various types of disease that could be treated with hematopoietic stem cell transplantation using purified blood CD34+ cells in both autologous and allogeneic settings. In autologous setting, unwanted cells such as lymphocytes or tumor cells should be depleted by the purification procedure. On the other hand, in allogeneic setting, the main purpose of purification will be an effective prophylaxis against graft-versus-host disease in the case of transplantation from HLA mismatched donors. During the study period, the projects were divided into three steps ; 1) establishment of mobilization and harvesting procedures, 2) clinical application of blood purified CD34+ cell transplantation as a new strategy, and 3) evaluation for long-term hematopoietic and immune recovery and maintenance after transplantation.In the first year, we compared the mobilization and harvesting efficacy of blood CD34+ … More cells between pediatric and adult donors. Then, we concluded that children could become more suitable donors for PBSC donation, because of less frequent adverse events by G-CSF injection, and more effectiveness in mobilization and harvesting procedures. In the next year, we successfully treated a patient with chronic inflammatory arthritis who was heavily depended on corticosteroids resulting in a short stature and suffering psychological problems. In this auto grafting, we confirmed that an immune suppressive therapy by high-dose cyclophosphamide and anti-lymphocyte globulin followed by purified blood CD34+ cells was effective and it continued over tow years. The function of the graft cells was also satisfactory from the aspects of both patients and donors.From the data, we concluded that a fraction of purified blood CD34+ cells was a useful stem cell source for transplantation in both autologous and allogeneic settings. This type of transplantation should be expanded into the new field of cell therapy. Less