Mesenchymal Stem Cell Exosomes for Periodontal Regeneration

用于牙周再生的间充质干细胞外泌体

基本信息

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
项目类别：
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

项目摘要

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

用于牙周再生的间充质干细胞外泌体项目概要/摘要牙周炎是一种由菌群失调引起的炎症性疾病，导致牙齿支持破坏复合体，包括牙骨质、牙周膜和牙槽骨。牙周组织的再生，虽然可行，但对临床医生来说仍然是一个巨大的挑战。间充质干细胞（MSC）在以下领域具有广阔的前景：再生医学。越来越多的证据表明间充质干细胞的再生作用很大程度上是由它们介导的分泌体。外泌体是大多数细胞类型分泌的纳米级脂质双层细胞器。外泌体已经作为一种通过转移其生物活性物质（包括 microRNA）来调节细胞间通讯（miRNA）。干细胞产生的外泌体已被证明具有与细胞产生的外泌体相当的治疗效果送货。然而，外泌体治疗在牙周再生中的潜力仍不清楚。在我们的初步研究中，我们分离并纯化了人骨髓间充质干细胞分泌的外泌体。这些外泌体是对受体细胞有促有丝分裂和趋化作用，还具有抗炎功能。不同的RNA特征是在 MSC 外泌体中发现，其中小 RNA 含量很高。通过RNA测序，我们进一步鉴定了一组外泌体中显着富集的 miRNA。因此，我们的数据强烈表明 MSC 外泌体可能是牙周病的潜在治疗剂。我们假设外泌体递送会促进牙周组织再生，这种作用可能是由富集的外泌体 miRNA 介导的。为了检验这个假设，我们将：1) 确定 MSC 外泌体的递送是否会促进实验性牙周炎模型中的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一种无细胞疗法来促进牙周再生。这项研究的结果将建立在支持 R01 拨款申请的初步数据将进一步阐明干细胞外泌体的安全性和有效性大型动物牙周病治疗和早期人体临床试验。也将帮助我们更好地了解外泌体诱导组织再生的机制，为未来的优化提供基础外泌体疗法。 1