Peripheral Tissue Antigen Display by Mesenchymal Stem Cells

间充质干细胞展示外周组织抗原

• 批准号: 8249440
• 负责人: Biju Parekkadan
• 金额: $ 13.8万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8249440
• 关键词: Adverse effects; Advisory Committees; Animal Model; Animals; Antigen Presentation; Antigen-Presenting Cells; Antigens; Atypical lymphocyte; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Automobile Driving; Award; Biodistribution; Biological Assay; Biomedical Engineering; Caring; Cell Communication; Cell Therapy; Cell Transplants; Cells; Chronic; Colitis; Colorectal; Crohn' s disease; Dependence; Development Plans; Disease; Disease model; Engineering; Engraftment; Epithelial; Future; General Hospitals; Goals; Granuloma; Hand; Health Care Costs; Heterogeneity; Human; Image; Immune; Immune response; Immunogenetics; Immunology; Immunotherapy; Impairment; In Situ; In Vitro; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Infusion procedures; Intestines; Lesion; Lymphocyte; Lymphoid; Lymphoid Tissue; Massachusetts; Medical; Medicine; Mentored Research Scientist Development Award; Mentorship; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Methods; Modeling; Molecular; Monitor; Morbidity - disease rate; Mus; Natural Immunity; Operative Surgical Procedures; Organ; Outcome; Patients; Peripheral; Pharmaceutical Preparations; Phenotype; Population; Postdoctoral Fellow; Predisposition; Prevalence; Prevention; Process; Proteins; Radiology Specialty; Relapse; Research; Research Personnel; Research Project Grants; Self Tolerance; Stem cells; T-Lymphocyte; Testing; Therapeutic; Therapy Clinical Trials; Tissues; Training; Transplantation; Treatment Efficacy; Ulcerative Colitis; Variant; adaptive immunity; base; career development; cell type; cellular imaging; gastrointestinal; imaging modality; in vivo; medical schools; molecular imaging; molecular/cellular imaging; pre-clinical; prevent; professor; programs; public health relevance; response; stem cell fate; stem cell therapy

DESCRIPTION (provided by applicant): The rationale driving this project is that there are natural cells in the body that are known to express peripheral tissue antigens (pTAs) and induce tolerance to self-reactive lymphocytes in vivo. We have discovered that MSCs also express these pTAs and can maintain this expression during ex vivo processing unlike other pTA expressing cells. We hypothesize that the expression of self antigens by MSCs is essential for the therapeutic efficacy of cell transplants in models of autoimmune disease, and therefore may be amenable to ex vivo monitoring/optimization to create a tailored cell therapy. The objectives are to evaluate the relevance of pTA expression in the immune response to MSCs, both in vitro and in vivo, and image these cell grafts during the treatment of an antigen-specific model of intestinal autoimmunity. The long-term goal is to evaluate this use of a unique form of antigen presentation by MSCs as a therapeutic mode of action and essentially create a new drug class based on antigen-specific stem cell grafts. PUBLIC HEALTH RELEVANCE: This is a Mentored Research Scientist Development Award application for Dr. Biju Parekkadan a biomedical engineer by training with specialization in cell-based therapy. He has developed new treatment approaches that harness the natural functions of mesenchymal stem cells (MSCs) for therapy. Recently, he has discovered a new function of MSCs that has significant relevance to the fields of autoimmunity and transplantation. As a recently appointed postdoctoral fellow, Dr. Parekkadan submits this five-year career development plan under the mentorship of Drs. Martin L. Yarmush, the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School and the director of the Center for Engineering in Medicine, Ralph Weissleder, Professor of Radiology at Harvard Medical School and the director of the Center for Molecular Imaging Research at the Massachusetts General Hospital and Diane Mathis, Professor of Immunology and Immunogenetics at Harvard Medical School. The award includes extensive: (1) hand-on training in radiological and immunological studies of cell transplants in vivo, (2) academic courses and seminars, and (3) guidance of a selected advisory committee towards the future large-scale research projects.

描述（由申请方提供）：驱动本项目的基本原理是，已知体内存在表达外周组织抗原（pTA）并诱导体内自身反应性淋巴细胞耐受的天然细胞。我们已经发现，MSC也表达这些pTA，并且与其他表达pTA的细胞不同，MSC可以在离体加工期间保持这种表达。我们假设MSC自身抗原的表达对于自身免疫性疾病模型中细胞移植的治疗功效是必不可少的，因此可以进行离体监测/优化以创建定制的细胞疗法。目的是评估pTA表达在体外和体内对MSC的免疫应答中的相关性，并在肠道自身免疫的抗原特异性模型治疗期间对这些细胞移植物进行成像。长期目标是评估MSC作为治疗作用模式的独特抗原呈递形式的这种用途，并基本上创建基于抗原特异性干细胞移植物的新药物类别。 公共卫生关系：这是Biju Parekkadan博士的指导研究科学家发展奖申请，他是一名生物医学工程师，接受过细胞治疗专业化培训。他开发了新的治疗方法，利用间充质干细胞（MSC）的天然功能进行治疗。最近，他发现了MSC的一种新功能，与自身免疫和移植领域有着重要的相关性。作为一名新任命的博士后研究员，Parekkadan博士在Martin L. Yarmush，哈佛医学院外科和生物工程学Helen Andrus Benedict教授，医学工程中心主任，Ralph Weissleder，哈佛医学院放射学教授，马萨诸塞州总医院分子成像研究中心主任，Diane马西斯，哈佛医学院免疫学和免疫遗传学教授。该奖项包括广泛的：（1）在体内细胞移植的放射学和免疫学研究方面的实践培训，（2）学术课程和研讨会，以及（3）为选定的咨询委员会提供指导，以促进未来的大规模研究项目。