HEMATOPOIETIC STEM CELLS TRANSPLANTATION

造血干细胞移植

• 批准号: 6202414
• 负责人: Robertson Parkman
• 金额: $ 20.04万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-29 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202414
• 关键词: Gaucher's disease; adenosine deaminase; adult human (21+); autologous transplantation; bone marrow; bone marrow transplantation; cell transplantation; enzyme deficiency; flow cytometry; gene expression; gene therapy; genetic manipulation; hematopoietic stem cells; human subject; human therapy evaluation; infant human (0-1 year); transfection /expression vector; umbilical cord

(Adapted from the applicant's abstract) Hematopoietic stem cells (HSC) can be used to treat patients with hematological, genetic, immunological and oncological diseases. To increase the number of patients potentially treated by HSC transplantation, we propose to investigate the use of genetically modified HSC (Gene Therapy) and highly purified HSC (CD34+, CD38- cells). Protocol 1 will evaluate gene therapy for infants with adenosine deaminase (ADA) deficiency and will compare two sources of HSC (cord blood and bone marrow) transduced under a single transduction protocol (daily retroviral supernatant addition in the presence of three growth factors for 72 hours) with an ADA containing retroviral vector. Protocol 2 will evaluate gene therapy for Gaucher disease in adult patients and will compare a single source of HSC (bone marrow) transduced under a single transduction protocol (daily retroviral supernatant addition in the presence of three growth factors for 72 hours) with an ADA containing retroviral vector. Protocol 2 will evaluate gene therapy for Gaucher disease in adult patients and will compare a single source of HSC (bone marrow) transduced under two transduction conditions (six hours incubation with retroviral supernatant without growth factors versus 72 incubation on autologous bone marrow stroma in the presence of retroviral supernatant) with a glucocerebrosidase containing retroviral vector. In both protocols patients will be evaluated for the presence of HSC engraftment in the absence of the administration of marrow ablative therapy. If HSC engraftment is achieved, the patients will be evaluated for expression of the transduced gene. Beside comparing the efficiency of the different transduction protocols, Protocols 1 and 2 will permit a comparison of the capacity of HSC from adults and children to engraft without marrow ablative therapy. Protocol 3 will determine the repopulating capacity of highly purified HSC (CD34+, CD38-cells) in patients who have received myeloid ablative chemotherapy. Patients will be monitored for the rapidity of hematopoietic reconstitution, and the clonality of their post-transplant hematopoiesis determined. Overall this proposal is an attempt to increase the number of patients treated by the transplantation of HSC by using techniques to isolate and/or genetically modify HSC.

（改编自申请人的摘要）造血干细胞（HSC） 可用于治疗血液学，遗传，免疫学的患者 和肿瘤疾病。增加患者的数量 通过HSC移植治疗，我们建议研究 转基因的HSC（基因治疗）和高度纯化的HSC（CD34+， CD38-细胞）。方案1将评估婴儿的基因治疗 腺苷脱氨酶（ADA）缺乏症，将比较HSC的两个来源 （脐带血和骨髓）在单个转导下转导 协议（在存在三个的每日逆转录病毒上清液 生长因子72小时），含有逆转录病毒载体的ADA。 协议2将评估成人Gaucher病的基因疗法 患者并将比较单一的HSC来源（骨髓） 在单个转导方案下转导（每日逆转录病毒 在存在三个生长因子的情况下，上清液增加了72 小时）与含有逆转录病毒载体的ADA。协议2将 评估成年患者Gaucher病的基因疗法，并将 比较在两个下转导的单个HSC（骨髓）的来源 转导条件（六小时与逆转录病毒孵育 没有生长因子的上清液与自体孵育72 在逆转录病毒上清液的存在下骨髓基质） 含有逆转录病毒载体的葡萄糖孢酶。在两个协议中 将评估患者的HSC植入 缺乏骨髓消融疗法的给药。如果HSC 植入了，将评估患者的表达 转导的基因。除了比较 不同的转导协议，协议1和2将允许A 比较成人和儿童植入的HSC的容量 没有骨髓消融疗法。协议3将确定 在高度纯化的HSC（CD34+，CD38细胞）中的重新流动能力 接受了髓样消融化疗的患者。患者会 受到造血重建的速度的监测， 其移植后造血的克隆性确定。全面的 该建议是试图增加治疗患者的数量 通过使用技术隔离和/或 基因修改HSC。