权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Establishment of hemopoietic cytokine therapy with a combination of hemopoietic factors for thrombocytopenia of childhood

造血因子联合治疗儿童血小板减少症的造血细胞因子疗法的建立

基本信息

批准号：
04454277
负责人：
KOMIYAMA Atsushi
金额：
$ 3.33万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

The present studies were conducted to establish hemopoietic cytokine therapy with a combination of hemopoietic factors for thrombocytopenia in several hematologic/neoplastic disorders of childhood. To make the better hemopoietic cytokine therapy, synergic effects of hemopoietic factors on the thrombopoiesis were first studied in the mouse and human culture systems using IL-3, IL-6, IL-11, G-CSF, GM-CSF, M-CSF, erythropoietin (EPO) and stem cell factor (SCF). Then, several combinations of hemopoietic factors were administered in children with aplastic anemia or acute leukemia.1. Synergic effects of hemopoietic factors in vitro(1) The stimulatory effects of IL-6 and IL-11 on the megakaryocyte colony formation were augmented by the addition of IL-3 in the mouse culture system.(2) In the human culture system, IL-6, IL-11 or SCF alone did not have the stimulatory effects on the megakaryocyte growth. When SCF was combined with IL-6 or IL-11, there was significant formation of megakaryocyte colonies. These results were confirmed in the experiments using CD34+ cells.(3) SCF had stimulatory effects on the proliferation of primitive megakaryocytic progenitors (megakaryocyte colony-stimulating factor) but not on the maturation of megakaryocytes (megakaryocyte potentiator). Thus, SCF should be administered in the clinical use in combination with such megakaryocyte potentiators as IL-6 and IL-11.(4) IL-3, IL-6, IL-11, GM-CSF, M-CSF or EPO alone or in combination could increase the megakaryocyte colony formation in some children with aplastic anemia.2. Hemopoietic cytokine therapy for thrombocytopenia(1) The administration of G-CSF, G-CSF + GM-CSF or G-CSF + EPO increased the number of platelets in some patients with aplastic anemia.(2) The effect of EPO to increase platelet counts was confirmed in the EPO therapy for anemia of prematurity.

目前的研究旨在建立联合造血因子的造血细胞因子疗法，用于治疗多种儿童血液/肿瘤疾病的血小板减少症。为了更好地进行造血细胞因子治疗，首先在小鼠和人类培养系统中利用IL-3、IL-6、IL-11、G-CSF、GM-CSF、M-CSF、促红细胞生成素（EPO）和干细胞因子（SCF）研究了造血因子对血小板生成的协同作用。然后，对患有再生障碍性贫血或急性白血病的儿童施用几种造血因子的组合。1．体外造血因子的协同作用(1)在小鼠培养体系中添加IL-3可增强IL-6和IL-11对巨核细胞集落形成的刺激作用。(2)在人培养体系中单独使用IL-6、IL-11或SCF对巨核细胞生长没有刺激作用。当SCF与IL-6或IL-11结合时，巨核细胞集落显着形成。这些结果在CD34+细胞的实验中得到了证实。(3)SCF对原始巨核细胞祖细胞的增殖有刺激作用(巨核细胞集落刺激因子)，但对巨核细胞的成熟没有刺激作用(巨核细胞增效剂)。因此，临床上应将SCF与IL-6、IL-11等巨核细胞增强剂联合使用。(4)IL-3、IL-6、IL-11、GM-CSF、M-CSF或EPO单独或联合使用，可增加部分再生障碍性贫血患儿的巨核细胞集落形成。2．血小板减少症的造血细胞因子治疗(1)G-CSF、G-CSF+GM-CSF或G-CSF+EPO使部分再生障碍性贫血患者血小板数量增加。(2)EPO增加血小板数量的作用在EPO治疗早产儿贫血中得到证实。