INTERPLAYS BETWEEN THE JAW MESENCHYMAL STEM CELLS AND T LYMPHOCYTES

颌间充质干细胞和 T 淋巴细胞之间的相互作用

基本信息

批准号：
7556796
负责人：
SONGTAO SHI
金额：
$ 41.56万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7556796
关键词：
Accounting Achievement Adipocytes Affect Apoptosis Bone Diseases Bone Marrow Cardiac Myocytes Cell Culture Techniques Cell Lineage Cell physiology Cells Characteristics Cherubism Chondrocytes Data Differentiation and Growth Disease Disease model Goals Immune Immune System Diseases Immune response Immunosuppression Immunosuppressive Agents Implant In Vitro Infusion procedures Interleukin-10 Jaw Knowledge Lead Link Lymphocyte Mediating Mesenchymal Stem Cells Mesoderm Methods Modality Molecular Multipotent Stem Cells Mus Myoblasts Nature Neural Crest Cell Neurons Northern Blotting Nude Mice Osteoblasts Osteogenesis Osteoporosis Pathway interactions Periodontal Diseases Periodontitis Phenotype Prevention Property Protocols documentation Regulation Role Staining method Stains Stem cells Syndrome Systemic disease T-Lymphocyte Testing Therapeutic Therapeutic Effect Time Tissues Transgenic Mice Western Blotting Work adult stem cell base bone design experience graft vs host disease improved in vitro activity in vivo innovation long bone mouse model novel novel strategies orofacial osteogenic response self-renewal skeletal disorder tissue regeneration trait tumor

项目摘要

DESCRIPTION (provided by applicant): Bone marrow mesenchymal stem cells (BMMSCs) are multipotent stem cells capable of differentiating into different lineage cells including osteoblasts, chondrocytes, adipocytes, cardiomyocytes, myoblasts, and neural cells. A recent major breakthrough was the discovery that BMMSCs exert a profound inhibitory effect on T cells. While our preliminary studies revealed that activated T cells are capable of inducing BMMSC apoptosis through the Fas/FasL pathway, suggesting a novel crosstalk mechanism between T cells and BMMSCs. Immune diseases target the orofacial bones with specific phenotypes as seen in periodontal diseases, cherubism, and hyperparathyroid jaw tumor syndrome. Moreover, the orofacial jaw bones contain MSCs (OFMSCs) that are distinct to BMMSCs in terms of differentiation traits and tissue regeneration characteristics. Therefore, the objective of this application is to explore whether and how T cells regulate OFMSCs and whether this regulation contributes to orofacial bone disorders. Our preliminary studies identified that we are able to isolate and expand mouse OFMSCs, which allow us to use mouse models to study the interplay between OFMSCs and T cells. This achievement is critical for the proposed studies because isolation and expansion of mouse OFMSCs are difficult and reliant on stem cell culture experience. Our preliminary data showed that mouse OFMSCs differ from BMMSCs in inhibiting T cell activities in vitro. Our hypothesis is that T cells regulate OFMSCs in a way distinctive from those discovered in the interplays between T cells and BMMSCs, which may link to the orofacial bone phenotypes of immune diseases. In this application, we will explore how T cells interplay with OFMSCs using BMMSCs as a comparison. Moreover, we will examine whether T cell-mediated OFMSC response involved in orofacial phenotypes of immune diseases such as T cell over-activated osteoporosis induced by ovarioectomy. Finally, we will assess whether systemic OFMSC infusion can offer therapeutic effect on T cell over-activated disorders. In summary, novel findings from our proposed studies will provide cellular and molecular basis for understanding interplays between T cells and OFMSCs. These data are likely to lead to new knowledge on identifying mechanisms of immune disorders associated with the orofacial bones. Project Narrative: The purpose of this study is to understand crosstalk between orofacial mesenchymal stem cells and immune cells and delineate the mechanisms by which the crosstalk may associate with orofacial bone diseases. We will use this knowledge to explore new approaches for orofacial bone disease treatment.

描述（由申请人提供）：骨髓间充质干细胞（BMMSC）是能够区分不同谱系细胞的多能干细胞，包括成骨细胞，软骨细胞，脂肪细胞，心肌细胞，肌细胞，肌细胞和神经细胞。最近的一个重大突破是BMMSC对T细胞产生深远的抑制作用。虽然我们的初步研究表明，活化的T细胞能够通过FAS/FASL途径诱导BMMSC凋亡，这表明T细胞和BMMSC之间具有新颖的串扰机制。免疫疾病针对牙周疾病，天使和甲状旁腺颌骨肿瘤综合征的特定表型的口面骨骼。此外，在分化性状和组织再生特征方面，口面颌骨包含与BMMSC不同的MSC（OFMSC）。因此，本应用的目的是探索T细胞是否以及如何调节MSC的调节以及该调节是否有助于口面骨疾病。我们的初步研究表明，我们能够隔离和扩展MSSC的小鼠，这使我们能够使用小鼠模型研究OFMSC和T细胞之间的相互作用。这项成就对于拟议的研究至关重要，因为MESS的隔离和扩展是困难的，并且依赖于干细胞培养的经验。我们的初步数据表明，在体外抑制T细胞活性方面，MSSC的小鼠与BMMSC有所不同。我们的假设是，T细胞以与T细胞和BMMSC之间相互作用的方式不同的方式调节了MSC的OFMSC，这可能与免疫疾病的口面骨表型联系起来。在此应用程序中，我们将使用BMMSCS作为比较，探索T细胞与OFMSC的相互作用。此外，我们将检查T细胞介导的MSC反应是否参与了免疫疾病的口面表型，例如T细胞过度激活的骨质疏松术是卵巢切除术引起的。最后，我们将评估系统性OFMSC输注是否可以对T细胞过度激活的疾病产生治疗作用。总而言之，我们提出的研究中的新发现将为理解T细胞与OFMSC之间的相互作用提供细胞和分子基础。这些数据可能会导致有关识别与口面骨相关的免疫疾病机制的新知识。项目叙述：这项研究的目的是了解口面间充质干细胞和免疫细胞之间的串扰，并描述串扰可能与口面骨疾病相关的机制。我们将使用这些知识来探索针对天质骨骼疾病治疗的新方法。