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：
7914377
负责人：
SONGTAO SHI
金额：
$ 39.75万
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 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914377
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 Regulatory T-Lymphocyte 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（申请人提供）：骨髓间充质干细胞（BMMSC）是能够分化成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、成肌细胞和神经细胞。最近的一项重大突破是发现 BMMSC 对 T 细胞具有深远的抑制作用。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 之间存在一种新的串扰机制。免疫疾病以具有特定表型的口面部骨为目标，如牙周病、天使病和甲状旁腺功能亢进颌骨肿瘤综合征。此外，口面部颌骨含有间充质干细胞（OFMSC），其在分化特征和组织再生特征方面与骨髓间充质干细胞不同。因此，本申请的目的是探讨 T 细胞是否以及如何调节 OFMSC，以及这种调节是否会导致口面部骨疾病。我们的初步研究表明，我们能够分离和扩增小鼠 OFMSC，这使我们能够使用小鼠模型来研究 OFMSC 和 T 细胞之间的相互作用。这一成就对于拟议的研究至关重要，因为小鼠 OFMSC 的分离和扩增很困难并且依赖于干细胞培养经验。我们的初步数据表明，小鼠 OFMSC 在体外抑制 T 细胞活性方面与 BMMSC 不同。我们的假设是，T 细胞调节 OFMSC 的方式不同于在 T 细胞和 BMMSC 之间相互作用中发现的方式，这可能与免疫疾病的口面部骨表型有关。在此应用中，我们将使用 BMMSC 作为比较，探讨 T 细胞如何与 OFMSC 相互作用。此外，我们将检查T细胞介导的OFMSC反应是否涉及免疫疾病的口面部表型，例如卵巢切除术引起的T细胞过度激活的骨质疏松症。最后，我们将评估全身性 OFMSC 输注是否可以对 T 细胞过度激活性疾病产生治疗作用。总之，我们提出的研究的新发现将为理解 T 细胞和 OFMSC 之间的相互作用提供细胞和分子基础。这些数据可能会带来关于识别与口面部骨骼相关的免疫疾病机制的新知识。项目叙述：本研究的目的是了解口面部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部骨疾病相关的机制。我们将利用这些知识探索口面部骨疾病治疗的新方法。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression.

间充质干细胞中炎症细胞因子诱导的细胞间粘附分子-1和血管细胞粘附分子-1对于免疫抑制至关重要。

DOI：
发表时间：
2010-03-01
期刊：
影响因子：
0
作者：
Ren, Guangwen;Zhao, Xin;Zhang, Liying;Zhang, Jimin;L'Huillier, Andrew;Ling, Weifang;Roberts, Arthur I;Le, Anh D;Shi, Songtao;Shao, Changshun;Shi, Yufang
通讯作者：
Shi, Yufang