Treatment of Periodontitis by Homing M2 Macrophages
Treatment of Periodontitis by Homing M2 Macrophages
批准号:
10437804
负责人:
CHARLES SFEIR
金额:
$46.87万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-07-01 至 2025-06-30
关键词:
AblationAddressAdoptive TransferAdultAffectAlveolar Bone LossAnti-Inflammatory AgentsAntibioticsBacterial InfectionsCalculiCardiovascular DiseasesCell SeparationCellsClinicalClinical TreatmentCommunitiesDataDebridementDental CalculusDental PlaqueDiabetes MellitusDiseaseDisease ProgressionEtiologyGeneticGingivaHarvestHelper-Inducer T-LymphocyteHomeostasisHomingImmuneImmune responseImmune systemInflammationInflammatoryInflammatory ResponseInterleukin-10Interleukin-4InterventionKnockout MiceLigandsLigatureLightMaxillaMethodsMicrobeMicrobial BiofilmsModalityModelingMouth DiseasesMusNatureNutrientPathogenesisPatientsPeriodicityPeriodontal DiseasesPeriodontitisPeriodontiumPhasePhenotypePlayPopulationPremature BirthPreventive therapyProcessPublic HealthRattusReportingResearchResolutionRoleSeveritiesStainsSumSystemSystemic diseaseTechnologyTestingTherapeuticTherapeutic EffectTherapeutic InterventionTissue HarvestingTissuesTooth LossTooth structureTranslatingUnited StatesWild Type Mouseagedbone losschemokinechronic inflammatory diseasecytokinedental biofilmdysbiosisexperimental studyfeasibility testingimmunoregulationin vivoinflammatory bone lossinsightmacrophagemicroCTmicrobialmicrobiotamonocytenovelnovel therapeutic interventionpathogenpreventrecruitrepairedresponsesingle-cell RNA sequencingstandard carestandard of caretumor-immune system interactions
中文摘要
牙周炎(PD)是第二常见的口腔疾病,影响着美国大约一半的成年人(6500万)
英文摘要
Periodontitis (PD) is the second most common oral disease, affecting about half of adults (65 millions) in the
United States. Periodontitis causes tooth loss and has been implicated in the pathogenesis of several serious
systemic diseases including diabetes, cardiovascular diseases, and premature birth. Periodontitis is a chronic
inflammatory disease, triggered by bacterial infection present in dental plaques and calculus; but actual disease
manifestations are caused by host immune response to these pathogens. Current standard treatment is
debridement of plaques and calculus to reduce the bacterial load; however, there are no therapies that address
the immune component of PD. Thus, many research groups have started developing technologies to regulate
the immune response and reduce inflammation. Our group has focused on recruiting and polarizing M2
macrophage as novel approaches for therapy of periodontitis. In our previous study, we successfully prevented
alveolar bone loss by locally inducing M2 macrophages in mouse periodontitis models. M2 macrophages were
polarized by injecting C-C motif chemokine 2 (CCL2) releasing PLGA microparticles (MPs) into periodontal
tissues. The results indicated that inducing M2 macrophages by local delivery of CCL2 indeed reduces
inflammation and bone loss in periodontitis. The proposed study will explore further the therapeutic potential of
M2 macrophage induction by CCL2 as well as shed light on the mechanism underlying this process. We
hypothesize that CCL2 plays a key role in maintaining periodontal immune homeostasis, and that its exogenous
delivery, or genetic ablation, would modify the course of PD through periodontal breakdown, repair and
microbiota dysbiosis. Macrophages play an important role in both the destructive and constructive phases of
the inflammatory response by modulating their ability to polarize into either M1 (pro-inflammatory/pro-destructive)
or M2 (anti-inflammatory/pro-reparative) macrophages. Our hypothesis is strongly supported by our recent in
vivo data showing that the local delivery of CCL2 will induce differentiation of macrophages and monocytes to
an M2 phenotype, thus leading to decreased periodontal inflammatory bone loss and initiation of periodontal
repair. To test this hypothesis, we propose the following specific aims: 1) To test CCL2 MPs as an interventional
and reparative periodontal therapy; 2) To study the periodontal phenotype, periodontal breakdown and repair in
CCL2-knockout mice (CCL2-KO); and 3) To perform Single cell RNA sequencing (ScRNA-Seq) to acquire in-
depth mechanistic data about the role of CCL2, its association, effect on and interactions with other immune
cells. We anticipate that CCL2 released from PLGA MPs will inhibit further bone loss and promote repair in the
mouse periodontitis model. We also expect that CCL2-KO mice and ScRNA-Seq analysis will provide data critical
to understanding underlying mechanisms of CCL2’s immunoregulatory effects. In sum, we believe that M2
macrophage induction by CCL2 in inflamed periodontium could be a novel, promising strategy for treating PD.
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Pittsburgh Craniofacial Sciences Training Program
-
批准号:10657807
-
项目类别:
-
资助金额:$11.05万
-
财政年份:2022
-
负责人:CHARLES SFEIR
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依托单位:
Pittsburgh Craniofacial Sciences Training Program
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批准号:10657803
-
项目类别:
-
资助金额:$35.56万
-
财政年份:2022
-
负责人:CHARLES SFEIR
-
依托单位:
Pittsburgh Craniofacial Sciences Training Program
-
批准号:10625702
-
项目类别:
-
资助金额:$10.84万
-
财政年份:2022
-
负责人:CHARLES SFEIR
-
依托单位:
Treatment of Periodontitis by Homing M2 Macrophages
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批准号:10649608
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项目类别:
-
资助金额:$47.29万
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财政年份:2020
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负责人:CHARLES SFEIR
-
依托单位:
Treatment of Periodontitis by Homing M2 Macrophages
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批准号:10197100
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项目类别:
-
资助金额:$47.01万
-
财政年份:2020
-
负责人:CHARLES SFEIR
-
依托单位:
Treatment of periodontitis by homing M2 macrophages
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批准号:9296130
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项目类别:
-
资助金额:$23.05万
-
财政年份:2016
-
负责人:CHARLES SFEIR
-
依托单位:
New Faculty for Craniofacial Tissue Engineering and Biology
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批准号:7858926
-
项目类别:
-
资助金额:$73.48万
-
财政年份:2009
-
负责人:CHARLES SFEIR
-
依托单位:
New Faculty for Craniofacial Tissue Engineering and Biology
-
批准号:7934057
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项目类别:
-
资助金额:$73.48万
-
财政年份:2009
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负责人:CHARLES SFEIR
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依托单位:
PROTEOMICS AND BIOMINERALIZATION OF DENTIN
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批准号:7892492
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项目类别:
-
资助金额:$12.19万
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财政年份:2006
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负责人:CHARLES SFEIR
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依托单位:
PROTEOMICS AND BIOMINERALIZATION OF DENTIN
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批准号:7148870
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项目类别:
-
资助金额:$12.19万
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财政年份:2006
-
负责人:CHARLES SFEIR
-
依托单位:
PROTEOMICS AND BIOMINERALIZATION OF DENTIN
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批准号:7452392
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项目类别:
-
资助金额:$12.19万
-
财政年份:2006
-
负责人:CHARLES SFEIR
-
依托单位:
PROTEOMICS AND BIOMINERALIZATION OF DENTIN
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批准号:7643254
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项目类别:
-
资助金额:$12.19万
-
财政年份:2006
-
负责人:CHARLES SFEIR
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依托单位:
PROTEOMICS AND BIOMINERALIZATION OF DENTIN
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批准号:7256212
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项目类别:
-
资助金额:$12.19万
-
财政年份:2006
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负责人:CHARLES SFEIR
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依托单位:
DENTIN BIOMINERALIZATION
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批准号:6816535
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项目类别:
-
资助金额:$31.24万
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财政年份:2004
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负责人:CHARLES SFEIR
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依托单位:
DENTIN BIOMINERALIZATION
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批准号:7069681
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项目类别:
-
资助金额:$29.25万
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财政年份:2004
-
负责人:CHARLES SFEIR
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依托单位:
DENTIN BIOMINERALIZATION
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批准号:7231485
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项目类别:
-
资助金额:$28.31万
-
财政年份:2004
-
负责人:CHARLES SFEIR
-
依托单位:
Novel Nano Calcium Phosphate for Pulp Gene Delivery
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批准号:6847471
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项目类别:
-
资助金额:$7.43万
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财政年份:2004
-
负责人:CHARLES SFEIR
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依托单位:
DENTIN BIOMINERALIZATION
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批准号:6918077
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项目类别:
-
资助金额:$30.07万
-
财政年份:2004
-
负责人:CHARLES SFEIR
-
依托单位:
Novel Nano Calcium Phosphate for Pulp Gene Delivery
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批准号:6790988
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项目类别:
-
资助金额:$7.44万
-
财政年份:2004
-
负责人:CHARLES SFEIR
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依托单位:
海外基金