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Peripheral Tissue Antigen Display by Mesenchymal Stem Cells

间充质干细胞展示外周组织抗原

基本信息

批准号：
8637989
负责人：
Biju Parekkadan
金额：
$ 13.06万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8637989
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&apos 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 gastrointestinal imaging modality in vivo in vivo imaging medical schools molecular imaging molecular/cellular imaging pre-clinical prevent professor programs public health relevance response stem cell fate stem cell therapy

项目摘要

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（由申请人提供）：推动该项目的基本原理是，体内存在已知表达外周组织抗原（pTA）并诱导体内对自身反应性淋巴细胞的耐受性的天然细胞。我们发现，与其他 pTA 表达细胞不同，MSC 也表达这些 pTA，并且可以在离体加工过程中维持这种表达。我们假设间充质干细胞表达自身抗原对于自身免疫性疾病模型中细胞移植的治疗效果至关重要，因此可能适合离体监测/优化以创建定制的细胞疗法。目的是在体外和体内评估 pTA 表达在 MSC 免疫反应中的相关性，并在肠道自身免疫抗原特异性模型治疗过程中对这些细胞移植物进行成像。长期目标是评估间充质干细胞独特形式的抗原呈递作为治疗作用模式的用途，并从本质上创建基于抗原特异性干细胞移植物的新药物类别。公共健康相关性：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，接受过细胞疗法专业培训。他开发了新的治疗方法，利用间充质干细胞 (MSC) 的自然功能进行治疗。最近，他发现了间充质干细胞的一个新功能，该功能与自身免疫和移植领域具有重要意义。作为最近任命的博士后研究员，Parekkadan 博士在 Drs. Parekkadan 的指导下提交了这份五年职业发展计划。哈佛医学院外科和生物工程海伦·安德鲁斯·本尼迪克特教授兼医学工程中心主任 Martin L. Yamush，哈佛医学院放射学教授兼马萨诸塞州总医院分子影像研究中心主任 Ralph Weissleder，以及哈佛医学院免疫学和免疫遗传学教授 Diane Mathis。该奖项包括广泛的：（1）体内细胞移植放射学和免疫学研究的实践培训，（2）学术课程和研讨会，以及（3）选定的咨询委员会对未来大规模研究项目的指导。