HUMAN CONCEPTAL TISSUE: CHARACTERIZATION FOR TRANSPLANT

这项建议的总体目标是继续我们对 胚胎组织移植的可用性和适宜性 研究和治疗。在本应用程序中，我们主要关注开发和 对收集、加工、冷冻保存方案的评估 胚胎来源的造血干细胞及其特性的研究 人的肝脏。详细研究将比较功能特征和 用常规的干细胞数据研究这些细胞的生长潜力 从成人骨髓中提取。特别努力还将致力于 捐赠者群体的捐献意愿分析 疾病传播的概念组织和风险因素的发生率， 以及评估捐赠的受孕组织是否符合严格的 美国纸巾银行协会制定的质量标准 (AATB)用于其他移植组织。 从胚胎肝脏中衍生出造血干细胞可能 代表着肿瘤学和治疗方面的重大进展 血液学疾病；包括治疗辐射引起的再生障碍性贫血。 造血干细胞移植，现在一般是自体的，是 已经在癌症化疗中广泛使用。胎儿移植 造血干细胞已经被证明可以导致完全的 部分严重联合免疫缺陷患者的重建 疾病和改善个人与各种其他 疾病，如再生障碍性贫血、白血病和代谢或储存 疾病，如高谢病。胚胎肝脏的使用是强有力的 由于造血干细胞的相对比例较高而受到青睐 与成人骨髓相比，T细胞所占比例较低 降低成人骨髓中发生移植物抗宿主反应的风险 移植。胚胎肝细胞也可能是更好的靶点 体细胞基因疗法。 参与这项申请的三所院校都有 概念的可获得性和适用性的协作研究 用于移植研究的组织。他们共同组成了西北 作为美国国立卫生研究院第一个胎儿受赠者的胎儿组织计划 组织银行项目。30多年来，中央实验室 人类胚胎学一直是美国国立卫生研究院保护的唯一国家资源 人类胚胎组织的收集、分析和分布。它有 收集和处理了超过15,000个胚胎和胎儿。西北地区 组织中心是组织银行的领导者。它得到了AATB的认可 专门从事各种移植和移植的冷冻保存 研究同种异体人体移植，包括自体和身体造血 干细胞。它是美国唯一一家组织银行， 加工、冷冻保存和分发如此广泛的同种异体 纸巾。骨髓替代疗法是在弗雷德大学开发的 西雅图哈钦森癌症研究中心，在那里研究和 干细胞替代的治疗应用正在进行中。把这些放在一起 机构提供了继续发展所需的广泛背景 来源的可移植细胞特性的相关研究 胚胎肝脏。

The overall goal of this proposal is continuation of our studies of the availability and suitability of embryonic tissue for transplantation research and therapy. In this application we focus on development and assessment of protocols for the collection, processing, cryopreservation and characterization of hematopoietic stem cells derived from embryonic human liver. Detailed study will compare functional characteristics and growth potential of these cells with data from stem cells conventionally prepared from adult bone marrow. Particular effort will also be devoted to analysis of the donor population with respect to willingness to donate conceptal tissues and incidence of risk factors for disease transmission, and to assessment of whether donated conceptal tissues meet rigorous quality standards developed by the American Association of Tissue Banks (AATB) for other transplanted tissues. Derivation of hematopoietic stem cells from embryonic liver could represent a major development in oncology as well as in the therapy of hematologic disorders; including treatment for radiation-induced aplasia. Hematopoietic stem cell transplantation, generally now, autologous, is already in widespread use in cancer chemotherapy. Transplantation of fetal hematopoietic stem cells has been shown to result in complete reconstitution of some patients with severe combined immunodeficiency disease and to improvement of individuals with a variety of other disorders like aplastic anemia, leukemia, and metabolic or storage disorders, like Gaucher's Disease. The use of embryonic liver is strongly favored because of the high relative percentage of hematopoietic stem cells compared to adult marrow and the low percentage of T-cells which reduces the risk of graft versus host reactions that occur in adult marrow transplantation. Embryonic liver cells may also be superior targets for somatic gene therapy. The three institutions participating in this application have a history of collaborative study of the availability and suitability of conceptal tissue for transplantation research. Together, they formed the Northwest Fetal Tissue Program that served as a grantee in the first NIH fetal tissue banking project. For over 30 years, the Central Laboratory for Human Embryology has been the only national resource fended by the NIH for collection, analysis and distribution of human conceptal tissue. It has collected and processed over 15,000 embryos and fetuses. The Northwest Tissue Center is a leader is tissue banking. It is accredited by the AATB and specializes in cryopreservation of a wide variety of transplant and research human allografts including autologous and cadaveric hematopoietic stem cells. It is the only tissue bank in the nation that procures, processes, cryopreserves and distributes such a wide range of allogeneic tissues. Bone marrow replacement therapy was developed at the Fred Hutchinson Cancer Research Center in Seattle, where research on and therapeutic use of stem cell replacement is ongoing. Together these institutions provide the breadth of background necessary for continued studies related to characterization of transplantable cells derived from embryonic liver.