Stem Cell and Transplantation Biology

干细胞和移植生物学

• 批准号: 10675711
• 负责人: DEREK L STIREWALT
• 金额: $ 63.28万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675711
• 关键词: Address; Adherence; Advisory Committees; Amendment; Animal Model; Area; Award; Biological Assay; Biological Products; Biology; Biomedical Research; CD34 gene; Canis familiaris; Cells; Charge; Chimerism; Collaborations; Communities; Consultations; Country; Development; Direct Costs; Disease model; Doctor of Philosophy; Dog Diseases; Educational workshop; Ensure; Faculty; Fee-for-Service Plans; Fred Hutchinson Cancer Research Center; Funding; Gene Expression; Gene Modified; Genes; Goals; Grant; Hematological Disease; Hematology; Hematopoiesis; Human; In Vitro; Income; Individual; Institution; Internships; Liquid substance; Logistics; Measurement; Measures; Mediating; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Nitrogen; Non-Malignant; Outcome; Patients; Persons; Pilot Projects; Positioning Attribute; Pre-Clinical Model; Procedures; Process; Production; Protocols documentation; Quality Control; Research; Research Personnel; Resources; Safety; Science; Services; Severe Combined Immunodeficiency; Shipping; Site; Speed; Spumavirus; Stem cell transplant; Training; Transplantation; Travel; Underrepresented Populations; Underrepresented Students; Underserved Population; Universities; Viral; Washington; Work; Xenograft procedure; base; canine model; cost; cost effective; data sharing; design; experience; gene therapy; genetic manipulation; graft vs host disease; in vivo; in vivo Model; in vivo evaluation; member; new technology; novel therapeutics; online community; organizational structure; outcome prediction; pre-clinical; prevent; programs; pyruvate kinase deficiency; quality assurance; recruit; stem cells; tool; transplant model; treatment response; virtual; web site

PROJECT SUMMARY/ABSTRACT - Overall The theme of this CCEH is focused on stem cell and transplantation biology. The aims are designed to overcome obstacles that prevent new investigators from joining this field. Specifically the four cores will provide investigators access to: Large numbers of human and canine stem/progenitor cells; Scalable viral production services for AAV, gamma-, lenti- and foamy viruses; Products for precision gene editing and functional genetic manipulation; PCR assays for tracking chimerism, and insertion sites; Xenografting to assess human hematopoiesis; Large animal model for preclinical in vivo testing and disease modeling. The major goal of this CCEH is to make these services available throughout the US. For this purpose, products and services must be cost- effective and of high quality. Also training in best practices for the use of these resources is imperative. Towards this goal core staff provide on-site training: funds to support travel to attend training sessions are available. In addition, standard operating procedures (SOP) and quality control measures (QC) for all processes and products are shared on our website where they can be discussed and amended as the science evolves. The logistics of distributing products throughout the country are challenging. However, since the first iteration of this grant (P30 DK056465) in 1999 we have successfully shipped highly purified CD34 cells in liquid nitrogen to hundreds of satisfied investigators. Our costs are generally less than 1/3 of the cheapest commercial vender, and our product is better. Logistics for shipping other biological products to out of state users are already in place. The fees for service charged by this CCEH generates program income of $1-2 million per year. These funds are used to increase staff, develop new technologies and to fund the Enrichment Program. The goal is to help build a strong, diverse, interactive hematology research community. Included in this effort is a research internship program for students from underrepresented or underserved populations. The Seattle CCEH research base consists of 25 faculty members at the University of Washington and/or the Fred Hutchinson Cancer Research Center. Currently our research base brings in $17,130,946 in direct costs per year for studies in non-malignant hematopoiesis.

项目总结/摘要-总体 本届CCEH的主题是干细胞和移植生物学。这些目标旨在 克服阻碍新调查人员加入这一领域的障碍。具体而言，四个核心将 为研究人员提供：大量的人类和犬干/祖细胞;可扩展的病毒 AAV、γ病毒、慢病毒和泡沫病毒的生产服务;用于精确基因编辑和 功能性遗传操作;追踪嵌合体和插入位点的PCR测定;异种移植， 用于临床前体内测试和疾病建模的大型动物模型。 该CCEH的主要目标是在美国各地提供这些服务。为此目的， 产品和服务必须具成本效益和高质素。此外，还进行了最佳做法培训， 这些资源是必不可少的。为实现这一目标，核心工作人员提供现场培训：资助差旅 参加培训课程。此外，标准操作程序（SOP）和质量 所有流程和产品的控制措施（QC）都在我们的网站上共享， 随着科学的发展而讨论和修改。 在全国范围内分销产品的物流具有挑战性。然而，自从第一次 在1999年，我们已经成功地将高度纯化的CD 34细胞运送到 给上百个满意的调查员我们的成本一般不到最便宜的1/3 商业供应商，我们的产品更好。运输其他生物制品到州外的物流 用户已经到位。 该CCEH收取的服务费每年产生100万至200万美元的方案收入。这些资金 用于增加工作人员，开发新技术和资助浓缩方案。目标是 帮助建立一个强大的，多样化的，互动的血液学研究社区。这项工作包括一项研究 为来自代表性不足或服务不足人口的学生提供实习计划。 西雅图CCEH研究基地由华盛顿大学和/或 弗雷德哈钦森癌症研究中心。目前，我们的研究基地带来了17，130，946美元的直接成本 非恶性造血研究。

项目成果

The canine gut microbiome is associated with higher risk of gastric dilatation-volvulus and high risk genetic variants of the immune system.

• DOI: 10.1371/journal.pone.0197686
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hullar MAJ;Lampe JW;Torok-Storb BJ;Harkey MA
• 通讯作者: Harkey MA

Fully human CD19-specific chimeric antigen receptors for T-cell therapy.

• DOI: 10.1038/leu.2017.57
• 发表时间: 2017-10
• 期刊: Leukemia
• 影响因子: 11.4
• 作者: Sommermeyer D;Hill T;Shamah SM;Salter AI;Chen Y;Mohler KM;Riddell SR
• 通讯作者: Riddell SR

Correction: Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.

修正：造血干细胞衍生的嵌合抗原受体 T 细胞在非人灵长类 HIV/AIDS 模型中的长期存在和功能。

• DOI: 10.1371/journal.ppat.1006891
• 发表时间: 2018
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Zhen,Anjie;Peterson,ChristopherW;Carrillo,MayraA;Reddy,SowmyaSomashekar;Youn,CindyS;Lam,BriannaB;Chang,NelsonY;Martin,HeatherA;Rick,JonathanW;Kim,Jennifer;Neel,NickC;Rezek,ValerieK;Kamata,Masakazu;Chen,IrvinSY;Zack,
• 通讯作者: Zack,

Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy.

• DOI: 10.1038/nbt.3461
• 发表时间: 2016-04
• 期刊: Nature biotechnology
• 影响因子: 46.9
• 作者: Liu L;Sommermeyer D;Cabanov A;Kosasih P;Hill T;Riddell SR
• 通讯作者: Riddell SR

Human Cord Blood and Bone Marrow CD34+ Cells Generate Macrophages That Support Erythroid Islands.

人脐带血和骨髓CD34+细胞产生支持红斑岛的巨噬细胞。

• DOI: 10.1371/journal.pone.0171096
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Belay E;Hayes BJ;Blau CA;Torok-Storb B
• 通讯作者: Torok-Storb B