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: 8053280
• 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/8053280
• 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(申请人提供)：这个项目的基本原理是人体内有自然细胞表达外周组织抗原(PTA)，并在体内诱导对自我反应性淋巴细胞的耐受。我们发现，与其他表达PTA的细胞不同，MSCs也表达这些PTA，并能在体外处理过程中保持这种表达。我们推测，MSCs自身抗原的表达对于细胞移植在自身免疫性疾病模型中的治疗效果是必不可少的，因此可能适合于体外监测/优化以创造一种量身定制的细胞疗法。我们的目的是评估PTA在体外和体内对MSCs的免疫反应中的相关性，并在抗原特异性的肠道自身免疫模型的治疗中对这些细胞移植进行成像。长期目标是评估MSCs将一种独特的抗原提呈形式作为一种治疗模式的使用，并从本质上创造一种基于抗原特异性干细胞移植的新药物类别。 公共卫生相关性：这是针对Biju Parekkadan博士的指导研究科学家发展奖申请，Biju Parekkadan博士是一名生物医学工程师，接受过细胞治疗方面的专门培训。他开发了新的治疗方法，利用间充质干细胞(MSCs)的自然功能进行治疗。最近，他发现了间充质干细胞的一种新功能，该功能与自身免疫和移植领域有重要关系。作为最近任命的博士后研究员，Parekkadan博士在哈佛医学院海伦·安德鲁斯·本尼迪克特外科和生物工程教授、医学工程中心主任Martin L.Yarmush博士、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Ralph Weissleder博士和哈佛医学院免疫学和免疫遗传学教授Diane Mathis的指导下提交了这份五年职业发展计划。该奖项包括广泛的：(1)活体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)一个选定的咨询委员会对未来大规模研究项目的指导。