HUMAN CONCEPTAL TISSUE: CHARACTERIZATION FOR TRANSPLANT

本提案的总体目标是继续研究 胚胎组织移植的可用性和适用性 研究和治疗。在这个应用程序中，我们专注于开发和 评估采集、处理、冷冻保存的方案 来源于胚胎干细胞的造血干细胞的鉴定和鉴定 人类肝脏详细的研究将比较功能特征， 这些细胞的生长潜力与常规干细胞的数据 由成人骨髓制成。还将特别努力 分析捐助者的捐助意愿 妊娠组织和疾病传播危险因素的发生率， 并评估捐赠的妊娠组织是否符合严格的 美国组织库协会制定的质量标准 （AATB）用于其他移植组织。 胚胎肝造血干细胞的来源 代表了肿瘤学以及肿瘤治疗的一个重大发展， 血液系统疾病;包括治疗辐射诱导的再生障碍。 造血干细胞移植，现在一般来说，自体的，是 已经在癌症化疗中广泛使用。胎儿移植 造血干细胞已经显示出导致完全的 某些重症联合免疫缺陷患者的重建 疾病和改善个人与各种其他 再生障碍性贫血、白血病、代谢或储存 疾病，如戈谢氏病。胚胎肝的使用 由于造血干细胞的相对百分比较高， 与成人骨髓相比， 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免疫抑制的上级靶点。 体细胞基因疗法 参与此次申请的三家机构， 概念的可用性和适用性的合作研究 用于移植研究的组织。他们一起形成了西北部 胎儿组织计划，作为第一个NIH胎儿 组织银行项目。30多年来，中央实验室 人类胚胎学是NIH资助的唯一国家资源， 收集、分析和分配人类胚胎组织。它有 收集并处理了超过15,000个胚胎和胎儿西北 组织中心是组织库的领导者。它是由AATB认证的 专门从事各种移植物的冷冻保存， 研究人类同种异体移植物，包括自体和尸体造血 干细胞它是全国唯一的组织库， 处理、冷冻保存和分配如此广泛的同种异体 组织中骨髓替代疗法是在弗雷德 位于西雅图的哈钦森癌症研究中心， 干细胞替代的治疗用途正在进行中。综合这些 机构提供了必要的背景，继续 与来自以下的可移植细胞的表征相关的研究 胚胎肝

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.