A microfluidic quality-control assay for stem-cell derived therapies
干细胞衍生疗法的微流体质量控制测定
基本信息
- 批准号:9045158
- 负责人:
- 金额:$ 32.5万
- 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:2016-03-21 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcademiaAddressAdoptionAnimal ExperimentsAnimalsBiological AssayBlood VesselsCell DensityCell Differentiation processCell LineCell LineageCell SurvivalClinicClinicalColony-Forming Units AssayDataData CollectionDevelopmentDevicesEmbryoEnvironmentEvaluationExtracellular MatrixFailureFutureGenerationsGerm LayersGoldGrowthHumanImmunodeficient MouseIn VitroIndustryInjection of therapeutic agentLeadLengthMedicineMethodsMicrofluidic MicrochipsMicrofluidicsModelingMusOperative Surgical ProceduresOrganOutputPatientsPerformancePhaseProcessProductionProtocols documentationQuality ControlReportingResearch PersonnelRunningSafetyStem Cell ResearchStem cellsStructureSystemTechnologyTeratomaTestingTimeTissue EngineeringTissuesTranslatingTranslationsTransplantationTumorigenicityVascularizationbasecell growthcell preparationcell typecommercializationcostdensitydesignhuman diseasehuman embryonic stem cellimplantationimprovedin vitro Assayin vitro Modelin vivoindexingmeetingspluripotencypre-clinicalpreventpublic health relevanceresearch and developmentresearch studyscreeningskillsstem cell therapysuccesstool
项目摘要
DESCRIPTION (provided by applicant): The emerging field of stem-cell therapy has the potential to transform medicine forever. However, a major bottleneck for bringing stem-cell therapies to the patient is the lack of adequate in-vitro assays for the study of stem-cell quality Critical test criteria are efficacy (pluripotency) prior to the differentiation process and safety lack of tumorigenicity) after differentiation prior to implantation of stem-cell derived tissues. The simplest assay available to assess stem-cell quality is the embryoid body (EB) assay. However, this assay is not able to support tissue growth long enough to achieve complete teratoma development. Therefore, the present gold standard for testing stem-cell quality relies on in vivo testing: by injecting stem-cell preparations into immunodeficient mice. This so-called "teratoma assay" assesses the stem cells' pluripotency, the ability to develop into cell types derived from all three embryonic germ layers. Unfortunately, this in-vivo assay has significant drawbacks: it requires a large number of animals, is prohibitively expensive, time consuming, labor- intensive, and results are dependent on surgical skills. The proposed project's objective is to develop an in-vitro assay based on a microfluidic chip containing a tissue-engineered, vascularized, humanized microenvironment for testing stem-cell pluripotency. Preliminary data obtained with the Nortis technology suggest that the proposed in-vitro model can perform the pluripotency test much more economically, and in a much shorter time frame than the in-vivo teratoma assay. Additionally, our data indicate that perfused microvasculature incorporated into stem-cell environment is key to long-term viability and differentiation of human teratoma tissue. During Phase I we will develop the microfluidic hardware and tissue-engineering protocols (Specific Aim 1). Additionally, we plan to demonstrate feasibility that the assay can be performed with a quality and robustness that complies with the requirements for assessing stem-cell pluripotency (Specific Aim 2). We will compare the performance of our teratoma chip directly with currently available methods, the EB assay and in-vivo teratoma assay. Minimum feasibility requirements for Phase I are to meet the performance quality and run time of the in- vivo assay, at significantly reduced costs. During Phase II we will dedicate major R&D to validate the assay and increase throughput capabilities. Ultimately, the proposed product will provide researchers in academia and industry with a powerful new in-vitro tool that will fuel the development of groundbreaking stem-cell therapies and their clinical translation.
描述(由申请人提供):干细胞治疗的新兴领域有可能永远改变医学。然而,将干细胞疗法带给患者的主要瓶颈是缺乏用于研究干细胞质量的适当体外测定。关键测试标准是分化过程之前的功效(多能性)和干细胞衍生组织植入之前的分化之后的安全性(缺乏致瘤性)。可用于评估干细胞质量的最简单的测定是胚状体(EB)测定。然而,该测定不能支持组织生长足够长的时间以实现完全的畸胎瘤发展。因此,目前测试干细胞质量的金标准依赖于体内测试:将干细胞制剂注射到免疫缺陷小鼠体内。这种所谓的“畸胎瘤检测”评估了干细胞的多能性,即从所有三个胚胎胚层发育成细胞类型的能力。不幸的是,这种体内测定具有显著的缺点:它需要大量的动物,非常昂贵,耗时,劳动密集,并且结果取决于手术技巧。拟议项目的目标是开发一种基于微流控芯片的体外检测方法,该芯片含有用于测试干细胞多能性的组织工程化、血管化、人源化微环境。用Nortis技术获得的初步数据表明,所提出的体外模型可以比体内畸胎瘤测定更经济地进行多能性测试,并且在更短的时间内进行。此外,我们的数据表明,灌注微血管纳入干细胞环境是人类畸胎瘤组织的长期生存能力和分化的关键。在第一阶段,我们将开发微流体硬件和组织工程协议(具体目标1)。此外,我们计划证明该试验的可行性,即该试验的质量和耐用性符合评估干细胞多能性的要求(具体目标2)。我们将比较我们的畸胎瘤芯片的性能直接与目前可用的方法,EB测定和体内畸胎瘤测定。阶段I的最低可行性要求是以显著降低的成本满足体内测定的性能质量和运行时间。在第二阶段,我们将致力于主要的研发,以验证分析和提高吞吐量的能力。最终,拟议的产品将为学术界和工业界的研究人员提供一个强大的新体外工具,这将推动开创性干细胞疗法及其临床转化的发展。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Thomas Neumann其他文献
Thomas Neumann的其他文献
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10210318 - 财政年份:2019
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