Mechanisms of Pro-Resolving Mediators in Periodontal Regeneration
牙周再生中促溶解介质的机制
基本信息
- 批准号:10674528
- 负责人:
- 金额:$ 46.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-05-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAnimal ModelAnimalsAnti-Inflammatory AgentsArachidonate 15-LipoxygenaseAttenuatedBiochemical ProcessBiochemistryBiomimeticsBone RegenerationCD59 AntigenCicatrixClinicalConnective TissueDentalDental CementumDevelopmental BiologyDietDiseaseDoseEnvironmentFamily suidaeFibrosisGoalsHost Defense MechanismHumanImmune responseIn VitroInflammationInflammatoryInflammatory ResponseKnowledgeLOX geneLipoxinsMacrophageMediatingMediatorMesenchymal Stem CellsMetabolismMolecular TargetNational Institute of Dental and Craniofacial ResearchNatural regenerationOrganPathway interactionsPeriodontal LigamentPeriodontitisPhenotypeProductionProliferatingPropertyPublishingResearchResolutionSignal PathwaySignal TransductionStrategic PlanningTestingTissue EngineeringTissuesTransplantationanalogbonebone healingcraniofacial tissuedesignenzyme biosynthesisexperimental studyhealinghuman diseaseimmunoregulationimprovedinjuredlipid biosynthesislipid mediatorlipoxin A4lipoxin B4microbiomenanoparticlenoveloral tissuepreclinical studyprogramsreceptor expressionreconstructionregeneration modelregenerativeresponsestem cell biologystem cell differentiationstem cell functionstem cell nichestem cell proliferationstem cell therapystem cellssynthetic enzymetherapeutic evaluationtissue injurytissue regenerationtranslation to humanstranslational approachwound healing
项目摘要
Project Summary
Uncontrolled inflammation is a major impediment to tissue engineering, regeneration and reconstruction of
both diseased and injured tissues resulting in further tissue injury, tissue scarring and fibrosis. Stem cell
activity is disrupted by persistent signals promoting inflammation, whereas specific anti-inflammatory signals
enhance stem cell activity. In successful regeneration, mesenchymal stem cells assume an anti-inflammatory
phenotype. Specialized Proresolving lipid Mediators (SPMS), including Lipoxin A4 (LXA4), attenuate the dental
stem cell inflammatory response. Resolution of inflammation is an active biochemical and metabolic process,
not merely a passive termination of inflammation, mediated by SPMs. SPMs activate wound healing with
tissue regeneration instead of fibrosis and scarring and directly improve bone healing and regeneration,
including in periodontitis. Human periodontal ligament stem cells release SPMs, including lipoxin, to regulate
immunomodulatory and pro-healing properties. Characterizing the biomimetic properties of SPMs in humans
is hampered by a lack of suitable large animal models. There is a critical need for a validated large animal
regeneration model to test therapeutic potential of SPMs for translation to humans. Our goal is to determine
the pathways to regeneration that control local inflammation and enhance mesenchymal stem cell
differentiation into connective tissues, including bone. The Central Hypothesis is that resolution of
inflammation pathways and mediators can promote regeneration of the periodontal organ (bone, cementum
and periodontal ligament) by directing stem cell phenotype, proliferation and differentiation. In this application,
we will use a large animal model to dissect the SPM pathways leading to periodontal ligament stem cell control
of regeneration. In this proposal, we will: 1: Provide direct evidence for SPM production by Yorkshire miniature
pig periodontal ligament stem cells (mpPDLSC) by determining the lipid mediator profile of mpPDLSC; 2:
Determine stem cell function in miniature pig by determining mpPDLSC proliferation and response to SPMs,
and determination of synthetic enzyme expression, signaling pathways and SPM receptor expression, and 3:
Demonstrate SPM enhanced stem cell mediated periodontal regeneration in Miniature Pigs using SPM local
delivery to enhance periodontal regeneration alone or in combination with transplanted, ex vivo expanded
miniature pig stem cells. Results from these studies will advance our practical clinical knowledge of dose and
delivery of lipoxins in tissue regeneration, identify potential new molecular targets, and further develop and
characterize a large animal model to test novel stem cell-based strategies for translation to human oral and
craniofacial tissue regeneration. The research team comprises experts in periodontal regeneration,
biochemistry, and large animal models.
项目摘要
炎症失控是组织工程、再生和重建的主要障碍。
病变和损伤的组织都会导致进一步的组织损伤、组织疤痕形成和纤维化。干细胞
活动被持续的促进炎症的信号干扰,而特定的抗炎信号
增强干细胞活性。在成功的再生过程中,间充质干细胞具有抗炎作用。
表型。包括脂氧素A4(LXA4)在内的专门的促分解脂质介体(SPMS)可以削弱牙齿
干细胞炎症反应。炎症的消退是一个活跃的生化和代谢过程,
不只是被动地终止炎症,由SPM介导。SPM通过以下方式促进伤口愈合
组织再生而不是纤维化和疤痕形成,并直接促进骨愈合和再生,
包括牙周炎。人牙周膜干细胞释放SPM,包括脂氧素,以调节
具有免疫调节和促进愈合的特性。SPM在人体内的仿生特性表征
由于缺乏合适的大型动物模型而受到阻碍。迫切需要一种经过验证的大型动物
再生模型,以测试SPM移植到人类的治疗潜力。我们的目标是确定
控制局部炎症和增强间充质干细胞的再生途径
分化成结缔组织,包括骨。中心假设是解决
炎症途径和介质可以促进牙周器官(骨、牙骨质)的再生
和牙周膜),通过指导干细胞的表型、增殖和分化。在此应用程序中,
我们将使用一个大型动物模型来解剖导致牙周膜干细胞控制的SPM通路。
重生的力量。在这项提案中,我们将:1:为约克郡微型公司生产SPM提供直接证据
猪牙周膜干细胞(MpPDLSC),通过测定mpPDLSC的脂质介质谱;2:
通过检测mpPDLSC的增殖和对SPMS的反应来确定小型猪的干细胞功能,
以及合成酶表达、信号通路和SPM受体表达的测定,以及3:
SPM局部增强干细胞介导的小型猪牙周再生
单独或与移植、体外扩增联合应用促进牙周再生
微型猪干细胞。这些研究的结果将促进我们对剂量和
脂氧素在组织再生中的传递,识别潜在的新分子靶点,并进一步开发和
描述一种大型动物模型,以测试基于干细胞的新策略,将其转化为人类口腔和
颅面组织再生。研究团队由牙周再生专家组成,
生物化学和大型动物模型。
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 }}
THOMAS Elliott VAN DYKE其他文献
THOMAS Elliott VAN DYKE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('THOMAS Elliott VAN DYKE', 18)}}的其他基金
Forsyth Postdoctoral Training in Oral Health Research
福赛斯口腔健康研究博士后培训
- 批准号:
10202556 - 财政年份:2017
- 资助金额:
$ 46.31万 - 项目类别:
Forsyth Postdoctoral Training in Oral Health Research
福赛斯口腔健康研究博士后培训
- 批准号:
9359313 - 财政年份:2017
- 资助金额:
$ 46.31万 - 项目类别:
Forsyth Postdoctoral Training in Oral Health Research
福赛斯口腔健康研究博士后培训
- 批准号:
10202558 - 财政年份:2017
- 资助金额:
$ 46.31万 - 项目类别:
Mechanisms of Pro-Resolving Mediators in Periodontal Regeneration
牙周再生中促溶解介质的机制
- 批准号:
10187544 - 财政年份:2015
- 资助金额:
$ 46.31万 - 项目类别:
Mechanisms of Resolvin E1 in Periodontal Regeneration
Resolvin E1 在牙周再生中的作用机制
- 批准号:
8861681 - 财政年份:2015
- 资助金额:
$ 46.31万 - 项目类别:
Mechanisms of Pro-Resolving Mediators in Periodontal Regeneration
牙周再生中促溶解介质的机制
- 批准号:
10439454 - 财政年份:2015
- 资助金额:
$ 46.31万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 46.31万 - 项目类别:
Grant-in-Aid for Early-Career Scientists