Endothelial Progenitor Cells for Assessing Toxicological Response Variability in
用于评估毒理学反应变异性的内皮祖细胞
基本信息
- 批准号:8620435
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-15 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAdultAffectAnimalsBiological AssayBiologyBlood CirculationBlood VesselsBlood VolumeCD34 geneCadmiumCell CountCell Culture TechniquesCell Differentiation processCell LineCell ProliferationCell SurvivalCellsCellular biologyChemicalsCollaborationsCost Effectiveness AnalysisCryopreservationCulture MediaDataDetectionDevelopmentDevelopmental ProcessDoseEndothelial CellsEnsureEvaluationFutureGenetic VariationGoalsHumanHuman GeneticsIn VitroIndividualIonizing radiationLegal patentLuciferasesMeasurementMediatingModelingNF-kappa BNeonatalNitric OxideNorth CarolinaOutcomePECAM1 genePopulationPopulation SciencesProductionPropertyReporterReproducibilityResearchResearch PersonnelRight-OnRisk AssessmentScientistSignal PathwaySignal Transduction PathwayStem cellsSubfamily lentivirinaeSubgroupTestingTimeToxic Environmental SubstancesToxicant exposureToxicity TestsToxicologyUniversitiesbasebisphenol Acell growthelectric impedancehazardhigh throughput screeningimmortalized cellinstrumentationnovelperipheral bloodpublic health relevanceresearch studyresponsescreeningtooltoxicant
项目摘要
Currently, toxicological risk assessment lacks direct estimation of the magnitude and variability of
human responses to environmental toxicants. Specifically, there is very little data on the effects of low
dose toxicants on human developmental processes, including cellular differentiation. That is because
the current basis of toxicological assessment, animals and immortalized cell lines, cannot adequately
model the impact of low level toxicant exposure on human population. A potential alternative
detection platform should enable incorporation of human variability in screening of a large number of
toxicants in a high-throughput manner. To establish such a platform, we suggest using human donor-
specific cells that can be (a) isolated in a non-invasive manner, (b) easily expanded in culture, and (c)
cryopreserved without loss of viability. We propose that human endothelial progenitor cells or
endothelial colony forming cells (ECFCs), a population of CD31+/CD34+ pluripotent cells found in
circulation, would fulfill these requirements. In vitro, ECFCs are highly proliferative and can
differentiate into mature endothelial cells (ECs). The overall goal of this research is to evaluate the
effect of chemical toxicants on viability, proliferation, and differentiation of ECFCs derived from
different individuals. Specifically in this proposal, we will determine the feasibility of ECFCs as a
platform for high-throughput chemical toxicity testing. For this purpose, we selected three known
environmental toxicants found at low levels in neonatal and adult peripheral blood: bisphenol A
(BPA), perfluorooctanoic acid (PFOA), and cadmium. The proposed study is the key step in the
development of a novel, robust, and comprehensive platform utilizing donor-specific pluripotent cells.
At the conclusion of this project, we will demonstrate the amenability of ECFC-based assays for high-
throughput evaluation of environmental toxicants. ECFC-based toxicological assays can become an
invaluable tool for functional assessment of human genetic diversity and identification of population
subgroups most vulnerable to chemical hazards.
目前,毒理学风险评估缺乏直接估计的幅度和可变性,
人类对环境毒物的反应具体来说,关于低血糖影响的数据很少
剂量毒物对人类发育过程,包括细胞分化。那是因为
目前毒理学评估的基础,动物和永生化细胞系,不能充分
模拟低水平毒物暴露对人类的影响。一个潜在的替代
检测平台应该能够在筛选大量的
以高通量的方式检测有毒物质。为了建立这样一个平台,我们建议使用人类捐赠者-
特异性细胞,其可以(a)以非侵入性方式分离,(B)在培养中容易扩增,和(c)
冷冻保存而不丧失活力。我们提出,人内皮祖细胞或
内皮集落形成细胞(ECFC),一群CD 31 +/CD 34+多能细胞,发现于
流通,将满足这些要求。在体外,ECFC是高度增殖的,
分化为成熟的内皮细胞(EC)。本研究的总体目标是评估
化学毒物对ECFC活力、增殖和分化的影响
不同的个体具体来说,在这项建议中,我们会研究把幼儿保育和教育中心作为
高通量化学毒性测试平台。为此,我们选择了三个已知的
在新生儿和成人外周血中发现低水平的环境毒物:双酚A
(BPA)全氟辛酸(PFOA)和镉。拟议的研究是
开发一种利用供体特异性多能细胞的新型、稳健和全面的平台。
在本项目结束时,我们将证明ECFC为基础的测定高,
环境毒物处理量评价基于ECFC的毒理学测定可以成为
人类遗传多样性功能评估和种群鉴定的宝贵工具
最容易受到化学危害的亚群体。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John William Ludlow其他文献
John William Ludlow的其他文献
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{{ truncateString('John William Ludlow', 18)}}的其他基金
Endothelial Progenitor Cells for Assessing Toxicological Response Variability in Humans
用于评估人类毒理学反应变异性的内皮祖细胞
- 批准号:
9149273 - 财政年份:2013
- 资助金额:
$ 24.9万 - 项目类别:
Endothelial Progenitor Cells for Assessing Toxicological Response Variability in Humans
用于评估人类毒理学反应变异性的内皮祖细胞
- 批准号:
9019006 - 财政年份:2013
- 资助金额:
$ 24.9万 - 项目类别:
Endothelial Progenitor Cells for Assessing Toxicological Response Variability in Humans
用于评估人类毒理学反应变异性的内皮祖细胞
- 批准号:
9301840 - 财政年份:2013
- 资助金额:
$ 24.9万 - 项目类别:
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