Mesenchymal Stem Cell Exosomes for Periodontal Regeneration

用于牙周再生的间充质干细胞外泌体

• 批准号: 9374725
• 负责人: Zhao Lin
• 金额: $ 15.5万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9374725
• 关键词: Address; Adult; Affect; Age; Alpha Cell; American; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antisense Oligonucleotides; Applications Grants; Behavior; Biogenesis; Bone Marrow; Caliber; Cell Communication; Cell Differentiation process; Cell Proliferation; Cell Therapy; Cells; Clinical Trials; Complex; Data; Dental Cementum; Dental General Practice; Development; Disease; Disease model; Distant; Economics; Embryonic Development; Encapsulated; Engineering; Engraftment; Environment; Exposure to; Foundations; Future; Genetic Transcription; Gingiva; Goals; Growth; Harvest; Histologic; Human; Immune; Immune response; Inflammation; Inflammatory; Knowledge; Lipid Bilayers; Mediating; Mediator of activation protein; Mesenchymal Stem Cells; MicroRNAs; Modality; Modeling; Natural regeneration; Oral; Oral cavity; Organ; Organelles; Outcome; Parents; Pathologic Processes; Pattern; Periodontal Diseases; Periodontal Ligament; Periodontitis; Periodontium; Physiological Processes; Population; Process; RNA; Regenerative Medicine; Rodent; Rodent Model; Role; Safety; Signal Transduction; Small RNA; Stem cells; Testing; Tetracyclines; Therapeutic; Therapeutic Agents; Therapeutic Effect; Tissues; Tooth Loss; Tooth structure; Transfection; Transportation; Vesicle; Wound Healing; X-Ray Computed Tomography; alveolar bone; angiogenesis; base; carcinogenesis; cell motility; cell type; exosome; immunoregulation; insight; intercellular communication; knock-down; microbial; microbiota; migration; novel; pleiotropism; prevent; public health relevance; reconstruction; regenerative; response; scaffold; small hairpin RNA; soft tissue; therapy outcome; tissue regeneration; transcriptome sequencing

Mesenchymal Stem Cell Exosomes for Periodontal Regeneration Project Summary/Abstract Periodontitis is an inflammatory disease caused by dysbiotic microbiota, leading to destruction of the tooth supporting complex, which includes the cementum, periodontal ligament and alveolar bone. Regeneration of the periodontium, although feasible, remains a great challenge to clinicians. Mesenchymal stem cells (MSCs) hold a great promise in regenerative medicine. Increasing evidence suggests that the regenerative effects of MSCs are largely mediated by their secretome. Exosomes are nanoscopic, lipid bilayer organelles secreted by most cell types. Exosomes have emerged as a novel modulator in intercellular communications through transfer of their bioactive cargos, which include microRNAs (miRNAs). Exosomes produced by stem cells have been shown to have comparable therapeutic outcomes to that of cell delivery. However, the potential of exosome therapy in periodontal regeneration is still unknown. In our preliminary studies, we isolated and purified exosomes secreted by human bone marrow mesenchymal stem cells. These exosomes were mitogenic and chemotactic to recipient cells and also had an anti-inflammatory function. Distinct RNA signatures were found in MSC exosomes, where small RNA was highly abundant. Through RNA sequencing, we further identified a group of miRNAs that was significantly enriched in exosomes. Therefore, our data strongly suggest that MSC exosomes may be a potential therapeutic agent for periodontal diseases. We hypothesize that exosome delivery will promote periodontal tissue regeneration and this effect may be mediated by the enriched exosomal miRNAs. To test this hypothesis, we will: 1) determine whether delivery of MSC exosomes will promote periodontal regeneration in an experimental periodontitis model in rodents; 2) investigate the role of miRNAs in exosome-mediated periodontal tissue regeneration. Our long term goal is to develop a cell-free therapy to promote periodontal regeneration. Results from this study will build on the body of preliminary data to support an R01 grant application that will further elucidate the safety and efficacy of stem cell exosome therapy for periodontal diseases in large animals and early human clinical trials. It will also help us better understand the mechanisms of exosome-induced tissue regeneration, which will provide a foundation for the future optimization of the exosome therapy. 1

间充质干细胞外泌体用于牙周再生 项目摘要/摘要 牙周炎是由失调菌群引起的炎症性疾病，导致牙齿支撑的破坏 复合物，包括牙骨质，牙周韧带和肺泡骨。牙周的再生， 尽管可行，但仍然是临床医生的巨大挑战。间充质干细胞（MSC）在 再生医学。越来越多的证据表明，MSC的再生作用主要由其介导 秘密。外泌体是大多数细胞类型分泌的纳米镜，脂质双层细胞器。外泌体已成为 通过转移其生物活性肉类，包括microRNAS的新型调制器在细胞间通信中 （miRNA）。干细胞产生的外泌体已被证明具有与细胞的治疗结局相当 送货。但是，外泌体治疗在牙周再生中的潜力仍然未知。在我们的初步研究中 我们分离了由人骨骨髓间充质干细胞分泌的和纯化的外泌体。这些外泌体是 有丝分裂和趋化对受体细胞的趋化性，并且具有抗炎功能。不同的RNA签名是 在MSC外泌体中发现，小RNA高度丰富。通过RNA测序，我们进一步确定了一组 在外泌体中显着富集的miRNA。因此，我们的数据强烈表明MSC外泌体可能是 牙周疾病的潜在治疗剂。我们假设外泌体递送将促进牙周组织 再生和这种作用可能是由富集的外泌体miRNA介导的。为了检验这一假设，我们将：1） 确定MSC外泌体的递送是否会在实验牙周炎模型中促进牙周再生 在啮齿动物中； 2）研究miRNA在外泌体介导的牙周组织再生中的作用。我们的长期目标是 开发无细胞的疗法以促进牙周再生。这项研究的结果将基于 初步数据支持R01赠款应用程序，该应用将进一步阐明干细胞外泌体的安全性和功效 大型动物和早期人类临床试验的牙周疾病的治疗。这也将帮助我们更好地了解 外泌体诱导的组织再生的机制，这将为未来优化的基础 外泌体治疗。 1