Core E: Xenografting

核心E：异种移植

• 批准号: 8566006
• 负责人: IRWIN D BERNSTEIN
• 金额: $ 13.59万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8566006
• 关键词: Age; Animal Husbandry; Animals; Bar Codes; Bioluminescence; Breeding; CD34 gene; Canis familiaris; Cells; Collaborations; Consult; Consultations; Engraftment; Experimental Designs; Growth Factor; Hematology; Hematopoiesis; Hematopoietic; Housing; Human; Image; Immune; Immunodeficient Mouse; Life; Marrow; Modeling; Mus; NOD/SCID mouse; Organ Transplantation; Population; Protocols documentation; Recombinants; Research; Research Personnel; Resources; SCID-hu Mice; Services; Site; Spleen; Stem cells; Teratoma; Tissue Sample; Transplantation; Work; Xenograft procedure; base; conditioning; fetal; immune function; in vivo; in vivo Model; induced pluripotent stem cell; investigator training; member; nonhuman primate; novel strategies; pre-clinical; programs; reconstitution; regenerative; stem

Human stem and progenitor cells have been shown to engraft in the marrow and spleen of sublethally irradiated NOD/SCID, sCID, Bg Nude/XID, NOD/SCID r chain""" (NSG) mice and in fetal organs xenografted in NOD/SCID (SCID/Hu) mice [1]. In some studies, optimal engraftment required administration of specific recombinant human growth factors [2]. Nevertheless, the demonstration of multilineage hematopoiesis in NOD/SCID mice transplanted with isolated human CD34+/CD38- "stem" cells supports the notion that xenogeneic transplantation in immunodeficient mice may serve as a surrogate model for human transplantation. Given the importance of preclinical in vivo models, the purpose of Core E is to provide CCEH members as well as other UW and FHCRC investigators with the resources and expertise needed to execute xenografting studies in immune deficient mice. The majority of studies involve analysis of hematopoietic reconstituting ability or immune function of defined populations of cells from humans, non-human primates, and dogs. Protocols have also been developed for evaluating the teratoma generating potential of ESC and iPSC, as well as the engraftment and regenerative potential of their derived progeny. Specifically Core E provides: 1) age appropriate NOD/SCID mice through an in-house breeding program, 2) expert consultation on experimental design, 3) help with obtaining lACUC approval, and 4) assistance with and/or full responsibility for conditioning and injecting mice, as well as sampling tissues from live and euthanized animals.

人类干细胞和祖细胞已被证明可以植入骨髓并 亚致死辐照的 NOD/SCID、sCID、Bg Nude/XID、NOD/SCID r 链“”” (NSG) 小鼠的脾脏以及 胎儿器官异种移植到 NOD/SCID (SCID/Hu) 小鼠中 [1]。在一些研究中，需要最佳的植入 施用特定的重组人生长因子[2]。尽管如此，示范 移植分离的人 CD34+/CD38-“干”细胞的 NOD/SCID 小鼠的多系造血 支持免疫缺陷小鼠的异种移植可以作为替代品的观点 人体移植模型。鉴于临床前体内模型的重要性，Core E 的目的 是为 CCEH 成员以及其他 UW 和 FHCRC 调查人员提供资源和 在免疫缺陷小鼠中进行异种移植研究所需的专业知识。大多数研究涉及 分析来自特定细胞群的造血重建能力或免疫功能 人类、非人类灵长类动物和狗。还制定了评估畸胎瘤的方案 ESC和iPSC的生成潜力，以及它们衍生的植入和再生潜力 后代。具体而言，Core E 提供：1) 通过内部育种提供适合年龄的 NOD/SCID 小鼠 计划，2) 实验设计专家咨询，3) 帮助获得 lACUC 批准，以及 4) 协助和/或完全负责调节和注射小鼠，以及从小鼠中取样组织 活的和安乐死的动物。