Specialized Proresolving Lipid Mediator-Enhanced Stem Cell Therapy and Tissue Regeneration
专门的溶解脂质介质增强干细胞治疗和组织再生
基本信息
- 批准号:10659020
- 负责人:
- 金额:$ 16.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-05 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccelerationAdoptedAffectAgonistAmericanAnabolismAnimal ModelAnimalsAnti-Inflammatory AgentsAreaAutologousBMP2 geneBacterial InfectionsBindingBiochemical ProcessBone MarrowBone TransplantationCD59 AntigenCellsChronicClinicalClinical TrialsComparative StudyCraniofacial AbnormalitiesDataDentalDentistsDevelopmentEnzyme Inhibitor DrugsEtiologyExhibitsExperimental ModelsFamily suidaeFundingGPR6 geneGoalsHealthHomeostasisHumanImmunologyInflammationInflammatoryInflammatory ResponseInjuryInvestigationKnowledgeLearningLeucine-Rich RepeatLipoxinsMediatingMediatorMentorsMentorshipMetabolismMissionNational Institute of Dental and Craniofacial ResearchNatural regenerationOperative Surgical ProceduresOralOsteoblastsPainPathologyPathway interactionsPeriodontal DiseasesPeriodontal LigamentPeriodontitisPeriodontiumPhasePopulationPositioning AttributePostdoctoral FellowProductionPropertyProteinsPublic HealthResearchResidenciesResolutionRoleScientistSignal TransductionStrategic PlanningSystemSystems BiologyTechnologyTestingTexasTissuesTooth TissueTrainingTranslational ResearchTranslationsTraumaUnited StatesUnited States National Institutes of HealthUniversitiesadult stem cellalveolar boneantagonistbiological systemsbonebone healingchronic inflammatory diseaseclinical practicecraniofacial complexcytokinedesigndysbiosisgene regulatory networkhealinghuman diseasehuman stem cellsimmunoregulationimplantationimproved outcomeinflammatory milieuinnovationlipid mediatornoveloral microbiomeosteogenicosteoprogenitor cellporcine modelpreferencereceptorregeneration modelregenerativeregenerative approachregenerative therapyregenerative tissueresponseself-renewalskillsstem cell biomarkersstem cell therapystem cellssuccesstherapeutic evaluationtissue regenerationtissue repairtranscriptome sequencingtranslation to humanstranslational potentialwound healing
项目摘要
PROJECT SUMMARY/ABSTRACT
Periodontal disease remains a significant public health problem. Chronic unresolved inflammation in response to proinflammatory oral microbiome dysbiosis induces host-mediated destruction of the periodontal tissues. Periodontal regeneration efforts have shown limited success due to the inability to resolve inflammation. Resolution of inflammation is initiated by Specialized Proresolving lipid Mediators (SPMs). SPMs include the lipoxins, resolvins, protectins, maresins, as well as their protein conjugates, which exhibit multipronged actions that improve the outcome of inflammation-related pathologies in experimental models and clinical trials. Human periodontal ligament stem cells human (PDLSC) release SPMs to regulate immunomodulatory and pro-healing properties. Among SPMs, Maresin 1 (MaR1) displays potent actions in regulating inflammation resolution and pain, wound repair and tissue regeneration. However, there is no defined mechanism by which MaR1 induces tissue regeneration, including bone. Our proposed research will address this gap by using a systems biology approach with LM-SPM metabolipidomics, and RNA-sequencing of PDLSC to discover possible pathways modulated by MaR1 in PDLSC tissue regeneration. By utilizing the American Yorkshire Pig as a large animal regeneration model, we will test the therapeutic potential of MaR1-enhanced PDLSC therapy for regeneration of periodontal tissues for translation to humans. Three specific aims are proposed: 1) To establish MaR1 biosynthetic pathway in PDLSC. 2) To define the mechanism by which MaR1 controls tissue regeneration. 3a) To demonstrate MaR1-enhanced PDLSC-mediated periodontal regeneration in the Pig. 3b) To elucidate the impact of MaR1 on combined BMP2-PDLSC treatment in the Pig. Results from these studies will address a mission of NIDCR: ”to support the development of human disease- and injury-relevant animal models for tissue regeneration of the oral and craniofacial complex, with preference given to large animal models.”
The candidate is a dentist-scientist and is currently a postdoctoral research fellow at the University of Texas Health San Antonio. This proposal includes a comprehensive mentorship and training plan to advance the candidate’s skills and knowledge in immunology, metabolipidomics, RNA-sequencing and translational science under the guidance of a strong team of NIH-funded scientists; Dr. Kenneth Hargreaves, Dr. Stephen Harris, Dr. Charles Serhan and Dr. George Huang. The proposal builds on the candidate’s previous research in stem cells, BMP2 and periodontium formation by integrating new areas of expertise. The plan includes a mentored phase designed to optimize learning and acquisition of new skills (K99) followed by the R00 phase, which is specifically designed to capitalize on the strengths of the applicant to develop a new path of research that will determine the role of resolution of inflammation and stem cells in BMP2 mediated regeneration. The R00 phase also includes residency training. Completion of this comprehensive training plan will position the candidate with a unique set of cross disciplinary skills that will enable her to transition to independence specializing in stem cell-based periodontal tissue regenerative therapies.
项目总结/摘要
牙周病仍然是一个重大的公共卫生问题。慢性未解决的炎症反应促炎性口腔微生物菌群失调诱导宿主介导的牙周组织破坏。由于无法解决炎症,牙周膜再生的努力已经显示出有限的成功。炎症的消退是由专门的促消退脂质介体(SPM)启动的。SPM包括脂氧素、消退素、保护素、maresins以及它们的蛋白质缀合物,它们在实验模型和临床试验中表现出改善炎症相关病理结果的多管齐下的作用。人牙周膜干细胞(PDLSC)释放SPM来调节免疫调节和促愈合特性。在SPM中,Maresin 1(MaR 1)在调节炎症消退和疼痛、伤口修复和组织再生中显示出有效的作用。然而,MaR 1诱导组织再生(包括骨)的机制尚不明确。我们提出的研究将通过使用LM-SPM代谢脂质组学的系统生物学方法和PDLSC的RNA测序来解决这一差距,以发现MaR 1在PDLSC组织再生中调节的可能途径。通过利用美国约克郡猪作为大型动物再生模型,我们将测试MaR 1增强的PDLSC疗法用于牙周组织再生的治疗潜力,以转化为人类。具体目标有三:1)建立牙周膜干细胞MaR 1生物合成途径。2)明确MaR 1控制组织再生的机制。3a)证明猪中MaR 1增强的PDLSC介导的牙周再生。3b)阐明MaRl对猪中BMP 2-PDLSC组合治疗的影响。这些研究的结果将解决NIDCR的使命:“支持开发人类疾病和损伤相关的动物模型,用于口腔和颅面复合体的组织再生,优先考虑大型动物模型。”
候选人是一名牙医科学家,目前是德克萨斯大学健康圣安东尼奥的博士后研究员。该提案包括一个全面的指导和培训计划,以提高候选人在免疫学,代谢脂质组学,RNA测序和转化科学方面的技能和知识,由NIH资助的科学家组成的强大团队指导; Kenneth Hargreaves博士,Stephen Harris博士,Charles Serhan博士和乔治Huang博士。该提案建立在候选人之前在干细胞,BMP 2和牙周组织形成方面的研究基础上,整合了新的专业领域。该计划包括一个指导阶段,旨在优化学习和获得新技能(K99),然后是R 00阶段,该阶段专门旨在利用申请人的优势开发一条新的研究路径,以确定炎症和干细胞在BMP 2介导的再生中的作用。R 00阶段还包括住院医师培训。完成这一全面的培训计划将使候选人具备一套独特的跨学科技能,使她能够过渡到独立从事基于干细胞的牙周组织再生疗法。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Audrey Rakian其他文献
Audrey Rakian的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Audrey Rakian', 18)}}的其他基金
Specialized Proresolving Lipid Mediator-Enhanced Stem Cell Therapy and Tissue Regeneration
专门的溶解脂质介质增强干细胞治疗和组织再生
- 批准号:
10429454 - 财政年份:2022
- 资助金额:
$ 16.31万 - 项目类别:
Bone Morphogenetic Protein Controls Links Between Dentinogenesis and Angiogenesis
骨形态发生蛋白控制牙本质发生和血管生成之间的联系
- 批准号:
8644652 - 财政年份:2013
- 资助金额:
$ 16.31万 - 项目类别:
Bone Morphogenetic Protein Controls Links Between Dentinogenesis and Angiogenesis
骨形态发生蛋白控制牙本质发生和血管生成之间的联系
- 批准号:
9042845 - 财政年份:2013
- 资助金额:
$ 16.31万 - 项目类别:
Bone Morphogenetic Protein Controls Links Between Dentinogenesis and Angiogenesis
骨形态发生蛋白控制牙本质发生和血管生成之间的联系
- 批准号:
8527448 - 财政年份:2013
- 资助金额:
$ 16.31万 - 项目类别:
Bone Morphogenetic Protein Controls Links Between Dentinogenesis and Angiogenesis
骨形态发生蛋白控制牙本质发生和血管生成之间的联系
- 批准号:
8831638 - 财政年份:2013
- 资助金额:
$ 16.31万 - 项目类别:
相似海外基金
How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
- 批准号:
2315783 - 财政年份:2023
- 资助金额:
$ 16.31万 - 项目类别:
Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
- 批准号:
2719534 - 财政年份:2022
- 资助金额:
$ 16.31万 - 项目类别:
Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2633211 - 财政年份:2020
- 资助金额:
$ 16.31万 - 项目类别:
Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
- 批准号:
20K01113 - 财政年份:2020
- 资助金额:
$ 16.31万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2436895 - 财政年份:2020
- 资助金额:
$ 16.31万 - 项目类别:
Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2633207 - 财政年份:2020
- 资助金额:
$ 16.31万 - 项目类别:
Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
- 批准号:
426559561 - 财政年份:2019
- 资助金额:
$ 16.31万 - 项目类别:
Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
- 批准号:
2236701 - 财政年份:2019
- 资助金额:
$ 16.31万 - 项目类别:
Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
- 批准号:
19K01745 - 财政年份:2019
- 资助金额:
$ 16.31万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
- 批准号:
415543446 - 财政年份:2019
- 资助金额:
$ 16.31万 - 项目类别:
Research Fellowships