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和 亚致死剂量照射的NOD/SCID、SCID、BG裸鼠/XID、NOD/SCID r链“”(NSG)小鼠和正常小鼠的脾 NOD/SCID(SCID/Hu)小鼠胚胎器官异种移植[1]。在一些研究中，需要最佳植入法 给予特定的重组人生长因子[2]。尽管如此， 分离的人CD34+/CD38-“干细胞”移植NOD/SCID小鼠的多系造血 支持免疫缺陷小鼠异种移植可作为替代物的观点 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 是为CCEH成员以及UW和FHCRC的其他调查人员提供资源和 在免疫缺陷小鼠身上进行异种移植研究所需的专业知识。大多数研究都涉及到 人外周血中特定细胞群的造血重建能力或免疫功能分析 人类、非人灵长类动物和狗。还开发了用于评估畸胎瘤的方案 ESC和IPSC的生成潜力及其衍生的植入和再生潜力 后代。具体地说，Core E通过内部饲养提供：1)适龄NOD/SCID小鼠 计划，2)试验设计专家咨询，3)帮助获得LACUC批准，4) 协助和/或全面负责小鼠的调理和注射，以及从 活体动物和安乐死动物。