Medhanism of EPC Dysfunction in the SS: Quantity over Quality
SS 中 EPC 功能障碍的机制:数量重于质量
基本信息
- 批准号:9357381
- 负责人:
- 金额:$ 4.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-19 至 2020-08-18
- 项目状态:已结题
- 来源:
- 关键词:AffectAgingAngiotensin IIAnimal ModelAnimalsAntibodiesAutologousBiological AssayBone MarrowCell Culture SystemCell TherapyCell membraneCell physiologyCell-Mediated CytolysisCellsChromosomesChromosomes, Human, Pair 13Clinical TrialsCompetenceComputer SimulationDataDevelopmentDiabetes MellitusDiabetic NeuropathiesDiseaseDoseExhibitsFunctional disorderGenesGoalsHeartHindlimbHormonesHumanHypertensionImpairmentIn VitroInfusion proceduresInjectableKiller CellsKnock-outLigand BindingLimb structureLongevityMasksMediatingMembraneMembrane ProteinsMicrovascular DysfunctionModelingMolecular ConformationMononuclearMyocardial InfarctionNK Cell ActivationNatural IncreasesNatural Killer CellsNatural regenerationOrganPathologicPatientsPeripheral arterial diseasePhysiologicalPopulationPredispositionProtein IsoformsProteomeRat StrainsRattusRattus norvegicusReceptor CellResearchRoleSmall Interfering RNAStem cellsStrokeTestingTherapeuticTimeTissuesTranscriptTreatment Efficacyadult stem cellangiogenesisbasecardiovascular risk factorconsomiccytotoxicityin vivoin vivo Modelkillingsknock-downmRNA Expressionoverexpressionperipheral bloodprotein structurereceptorrepairedrestorationsalt sensitive hypertensionstem cell therapyvector-induced
项目摘要
Project Summary
Endothelial progenitor cells (EPCs) are adult stem cells with roles in angiogenesis and endothelial
function. Human and animal studies suggest that autologous stem cell therapy using an EPC enriched
population of cells can be therapeutic in diseases such as hypertension, myocardial infarction, stroke, and
diabetes. However, EPCs from diseased and aging hosts show decreases in number and function that are
likely to compromise therapeutic efficacy, thus masking the potential of EPC based therapy. The objective of
this study is to determine the mechanism of impaired angiogenic competency of EPCs in an animal model of
EPC dysfunction. In the proposed animal model, the SS/MCWi (SS) rat, EPC competency and longevity is
impaired in vivo but rescued in vitro. We have observed an increase in the natural killer (NK) cell receptor 2B4
(CD244) on the membrane of SS EPCs and an increase in killing of SS EPCs by SS NK cells. We
hypothesize that increased expression of CD244 on the EPC membrane leads to increased NK cell
mediated destruction of SS EPCs in vivo, which compromises their ability to induce angiogenesis. We
will use an in vitro cytotoxicity assay and an in vivo model of hind-limb angiogenesis to test the effects of
CD244 knockdown and NK cell depletion on NK cell mediated destruction and angiogenic competency of SS
EPCs. We will also assess the physiological impact of the various observed CD244 transcript sequences in an
in vitro cell culture system. Because we have previously shown that low-dose angiotensin II (AngII) restores
angiogenesis in SS rats and angiogenic competency in SS bone marrow mononuclear cells, we will assess the
effects of AngII on the angiogenic competency, CD244 expression, and NK cell mediated cytotoxicity of SS
EPCs.
项目总结
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)
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{{ truncateString('Eric c Exner', 18)}}的其他基金
Medhanism of EPC Dysfunction in the SS: Quantity over Quality
SS 中 EPC 功能障碍的机制:数量重于质量
- 批准号:
9751926 - 财政年份:2016
- 资助金额:
$ 4.61万 - 项目类别:
Medhanism of EPC Dysfunction in the SS Rat: Quantity over Quality
SS 大鼠 EPC 功能障碍的机制:数量重于质量
- 批准号:
9192086 - 财政年份:2016
- 资助金额:
$ 4.61万 - 项目类别:
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