PROLIFERATION AND DIFFERENTIATION OF STEM CELLS

干细胞的增殖和分化

• 批准号: 3163405
• 负责人: PETER M MAUCH
• 金额: $ 38.54万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163405
• 关键词: Hodgkin's disease; X ray; bleomycin; bone marrow transplantation; cell death; cell differentiation; cellular oncology; colony stimulating factor; combination cancer therapy; cyclophosphamide; drug adverse effect; erythrocytes; erythropoiesis; graft versus host disease; hematopoiesis; hematopoietic growth factor; hematopoietic stem cells; human subject; human therapy evaluation; immunofluorescence technique; leukocyte activation /transformation; lymphocyte; methotrexate; myeloid stem cell; myeloproliferative neoplasm; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; nitrogen mustard; procarbazine; radiation dosage; radiation therapy dosage; radiobiology; radiotracer; relative biological effectiveness; scintillation counter; synchronous cell division; tissue /cell culture; tumor antigens; vinblastine

These studies continue to evaluate the effects of radiation therapy and chemotherapy as they relate to the organization of the hematopoietic stem cell compartment and to bone marrow transplantation (BMT). The bone marrow is an important dose limiting cell renewal tissue for both wide field irradiation and chemotherapy. These studies will explore the number and pedigree of the cells transplanted as these parameters relate to engraftment, survival and long term hematopoietic function in recipient animals. This should allow further definition of the limited proliferative capacity of the bone marrow stem cell compartment. Two of the major problems in BMT are minimizing the potential toxicities of preparing the recipient for transplantation while continuing to optimize long term engraftment. High dose cyclophosphamide and total body irradiation (TBI) are used by most centers to prepare recipients for BMT although busulfan has been substituted for TBI in some institutions. The organ specific toxicities of TBI and busulfan will be compared. Experiments will evaluate whether the addition of cyclophosphamide will allow reduction in the doses of TBI or busulfan required to maintain engraftment at equivalent or lower toxicity as compared to the use of TBI or busulfan alone. Engraftment and survival decrease following transplantation of T cell depleted marrow as the genetic differences between host and recipient increase. The role of accessory cells and factor secretion in the positive regulation of engraftment across varying genetic barriers will be studied. Resistance to engraftment may also be mediated by residual recipient marrow cells and alternative transplantation regimens to treat the recipient marrow will be tested. These will include increasing the dose of TBI, the addition of cytotoxic agents along with TBI, and the treatment of recipient animals with monoclonal antibodies to T cells or natural killer cells along with TBI. Alternative treatment of the recipient will be considered both to improve engraftment of T depleted marrow as well as to minimize the toxicity of TBI. All of these studies should allow improvement of engraftment through alterations in the marrow or in preparation of the recipient.

这些研究继续评估辐射的影响 与组织有关的治疗和化学疗法 造血干细胞室和骨髓 移植（BMT）。 骨髓是重要的剂量 限制细胞更新组织，以进行广阔的场照射和 化学疗法。 这些研究将探讨数量和 这些参数与移植的细胞的血统相关 植入，生存和长期造血功能 接受动物。 这应该可以进一步定义 骨髓干细胞的增殖能力有限 车厢。 BMT中的两个主要问题正在最小化 准备接收者的潜在毒性 移植同时继续优化长期 植入。 高剂量环磷酰胺和总体 大多数中心使用辐照（TBI）来准备接收者 对于BMT，尽管Busulfan已在某些人中取代了TBI 机构。 TBI和Busulfan的器官特异性毒性将 比较。 实验将评估是否添加 环磷酰胺将允许降低TBI剂量或 将植入物保持在同等或较低的 与仅使用TBI或Busulfan相比，毒性。 t移植后植入和存活率下降 细胞耗尽的骨髓作为宿主和宿主之间的遗传差异 接受者增加。 辅助细胞和因子的作用 分泌在各种不同的植入的正调节中 将研究遗传障碍。 抵抗植入可能 还由残留受体骨髓细胞和 替代移植方案以治疗接受者 骨髓将进行测试。 这些将包括增加剂量 TBI，添加细胞毒性剂与TBI，以及 用单克隆抗体的t处理受体动物 细胞或天然杀伤细胞以及TBI。 替代治疗 接收者的既可以改善植入 t耗尽的骨髓以及最小化TBI的毒性。 所有这些研究应允许改善植入 通过改变骨髓或准备 接受者。