Development and Maintenance of Thymic Epithelial Microenvironments

胸腺上皮微环境的发展和维持

基本信息

批准号：
8527705
负责人：
MARK PEZZANO
金额：
$ 32.36万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8527705
关键词：
Address Adipocytes Adult Architecture Atrophic Biological Models Blood Bone Marrow Bone Marrow Transplantation Cancer Patient Cell Communication Cell Line Cell Maintenance Cell physiology Cell surface Cells Characteristics Chondrocytes Clinical Coculture Techniques Development Disease Engraftment Epithelial Exhibits Fluorescence Gene Expression Genes Genetically Engineered Mouse Growth Hematological Disease Hematopoiesis Hematopoietic Hematopoietic stem cells Histones Homeostasis Human Immune Immune system In Vitro Infection Injection of therapeutic agent Integrins Kidney Label Lead Life Location Maintenance Malignant - descriptor Malignant Neoplasms Maps Mesenchymal Mesenchymal Stem Cells Minority-Serving Institution Morbidity - disease rate Mouse Strains Natural regeneration Non-Malignant Nude Mice Operative Surgical Procedures Osteoblasts Patients Phenotype Population Population Heterogeneity Productivity Property Proteins Puberty Publications Recovery Recruitment Activity Relapse Reporter Research Research Personnel Role Signal Pathway Signal Transduction Skin Sorting - Cell Movement Stem Cell Factor Stem cell transplant Stem cells Structure Students T-Cell Development T-Lymphocyte TACSTD2 gene Testing Thymic Tissue Thymic epithelial cell Thymus Gland Time Tissues Training Transgenic Mice Transgenic Model Translations Transplantation United States National Institutes of Health adaptive immunity adult stem cell base bone cancer therapy capsule design fighting functional loss immune function improved in vivo inhibitor/antagonist mouse model novel pluripotency postnatal premature progenitor public health relevance reconstitution response self-renewal stem cell population treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Development and maintenance of a properly functioning immune system is dependent upon a properly organized and functioning thymus. Thymic epithelial cells (TECs) make up the structure of the thymus and are responsible for the maintaining its primary functions. Bone marrow transplants can cure many forms of blood-derived cancers as well as non-malignant blood disorders. Unfortunately, particularly in adult patients, bone marrow transplants damage the thymus and in particular TECs resulting in a reduced capacity to fight infection and cancer. Stem cells in a variety of tissues have been identified by their capacity to divide very slowly, the so-called "label retaining cells" (LRCs). A novel genetically engineered mouse model system, which allows identification and purification of viable Histone 2B-green fluorescence protein tagged stem cells and was successfully used to identify and purify skin stem cells, has been used here to purify thymic epithelial stem cells. Preliminary results show that surgical transfer of these cells under the kidney capsule results in the formation of functional thymic tissue. The aims of this study will be to: 1) further characterie the recently identified thymic epithelial stem cells with the ability to reform thymic tissue; 2) understand the signals and cell to cell interactions that control the maintenance of adult thymic stem cells; 3) test the capacity of thymic stem cells and recently developed stem cell lines to enhance the recovery of thymic function in a mouse model of bone marrow transplant. These studies will be instrumental in the design of new clinical strategies to counteract thymic involution as well as the premature thymic degeneration that occurs in response to cancer treatments and BMT. From a developmental standpoint this study will allow the PI to continue to train underserved research students, while enhancing both the scientific productivity of the lab and the impact of the publications produced, enabling a researcher at a minority serving institution to be more competitive for NIH support.

描述（由申请人提供）：适当运行的免疫系统的开发和维护取决于正确组织和运行的胸腺。胸腺上皮细胞（TEC）构成胸腺的结构，并负责维持其主要功能。骨髓移植可以治愈多种形式的血液衍生癌症以及非恶性血液疾病。不幸的是，尤其是在成年患者中，骨髓移植会损害胸腺，尤其是TEC，导致对抗感染和癌症的能力降低。各种组织中的干细胞已经通过它们的能力非常缓慢地鉴定出所谓的“标记保留细胞”（LRCS）。一个新型的基因工程小鼠模型系统，允许鉴定和纯化可行的组蛋白2B绿色荧光蛋白标记的干细胞，并成功地用于识别和纯化皮肤干细胞，以纯化胸腺上皮干细胞。初步结果表明，这些细胞在肾囊下的手术转移导致功能性胸腺组织的形成。这项研究的目的是：1）进一步特征最近确定的胸腺上皮干细胞具有改革胸腺组织的能力； 2）了解控制成年胸腺干细胞维持的细胞相互作用的信号和细胞； 3）测试胸腺干细胞的能力，并最近开发了干细胞系以增强骨髓移植小鼠模型中胸腺功能的恢复。这些研究将有助于设计新的临床策略，以抵消胸腺疾病的相关性以及响应癌症治疗和BMT的过早胸腺变性。从发展的角度来看，这项研究将使PI能够继续培训服务不足的研究学生，同时提高实验室的科学生产力和所产生的出版物的影响，从而使少数民族的研究人员能够为NIH支持提供更具竞争力。