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

• 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
• 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

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。最近的一个重大突破是发现BMMSC对T细胞产生深刻的抑制作用。而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，提示T细胞与BMMSC之间存在一种新的串扰机制。免疫性疾病以具有特定表型的口面骨为目标，如牙周病、巨颌症和甲状旁腺亢进性颌骨肿瘤综合征。此外，口面颌骨中含有间充质干细胞（OFMSCs），在分化特性和组织再生特性方面与BMMSCs不同。因此，本申请的目的是探索T细胞是否以及如何调节OFMSC，以及这种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。这一成就对于所提出的研究至关重要，因为小鼠OFMSC的分离和扩增是困难的，并且依赖于干细胞培养经验。我们的初步数据表明，小鼠OFMSCs在体外抑制T细胞活性方面不同于BMMSCs。我们的假设是，T细胞调节OFMSCs的方式不同于那些发现在T细胞和BMMSCs之间的相互作用，这可能与免疫疾病的口面骨表型。在本申请中，我们将探索T细胞如何与OFMSC相互作用，使用BMMSC作为比较。此外，我们将研究T细胞介导的OFMSC反应是否参与免疫性疾病的口面表型，如T细胞过度激活的卵巢切除术诱导的骨质疏松症。最后，我们将评估系统性OFMSC输注是否可以对T细胞过度活化疾病提供治疗效果。综上所述，本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。这些数据可能会导致新的知识识别机制的免疫疾病与口面骨。项目叙述：本研究的目的是了解口腔颌面部间充质干细胞和免疫细胞之间的串扰，并描绘串扰可能与口腔颌面部骨疾病的机制。我们将利用这些知识来探索口面骨疾病治疗的新方法。

项目成果

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

• DOI: 10.4049/jimmunol.0902023
• 发表时间: 2010-03-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Ren G;Zhao X;Zhang L;Zhang J;L'Huillier A;Ling W;Roberts AI;Le AD;Shi S;Shao C;Shi Y
• 通讯作者: Shi Y