Engineering the Organizer
设计组织者
基本信息
- 批准号:10317741
- 负责人:
- 金额:$ 22.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-15 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAdultAmphibiaAnteriorAutomobile DrivingBedsBiologicalBiological AssayBiological ModelsBiomedical ResearchBiophysicsCell DensityCell Differentiation processCellsCellular biologyCentrifugationClinicClinical ResearchComplexCoupledDevelopmentDiseaseDorsalEmbryoEmbryonic DevelopmentEmbryonic OrganizersEngineeringEthicsExposure toFibroblast Growth FactorFutureGastrulaGenesGeometryGoalsGrowth FactorHumanHuman DevelopmentHuman bodyLeftManualsMapsMechanicsMethodsModelingModernizationMorphogenesisMorphologyMovementNatural regenerationNobel PrizeNodalOrganOrganogenesisOrganoidsOutcomePathway interactionsPatternPlanet EarthPositioning AttributeProcessProtocols documentationPublishingRanaRecombinant Growth FactorRegenerative MedicineShapesSignal TransductionSiteSorting - Cell MovementSourceSpecific qualifier valueSpeedSpemann&aposs OrganizerStructureSystemTechniquesTechnologyTestingThinnessTissue EngineeringTissuesTranslatingUndifferentiatedWorkXenopusXenopus laevisbasebioprintingblastomere structurecell behaviorcell typeclinically relevantdensitydesignembryo tissueexperienceexperimental studyexposure pathwayhuman embryonic stem cellhuman tissueinduced pluripotent stem cellinnovationmagnetic fieldmechanical propertiesnew technologynovelprogramsprototypescaffoldself assemblystem cell modelsynthetic constructthree dimensional structuretooltranslation to humanstumor progression
项目摘要
Project Summary:
Regeneration and development operate on the sub-millimeter scale, using evolved design principles to
drive self-assembly of replacement and new organs. Our goal with this project is to follow the principle of
'the organizer', where a small group of cells are microsurgically grafted into a naive host tissues to pattern and
induce organ primordia from the naive tissue. To achieve this we first identify methods to produce stable
laminar sheets of naive tissue (i.e. stable host tissues), and to develop novel tools to assemble these laminar
sheets, (i.e. in place of manual microsurgical grafts) to enable formation of planar polarized 3D structures. The
principles that propel modern tissue engineering are based on classic embryological studies of morphogenesis
in organoids. These classic studies relied on amphibian models where specified cells could be isolated from
embryos, formed into aggregates, and differentiated into distinctive tissues. Following programs of sorting and
engulfment, and differentiation, cells self-assemble planar, polarized laminar sheets with distinct polarity, e.g.
anterior-to-posterior, to form tissues consisting of multiple cell types at high cell density. It is now widely
recognized that similar, conserved programs of self-assembly shape human tissues during embryogenesis,
regeneration, and cancer progression. However, current efforts to engineer complex 3D structures suffer from
an inability to reproducibly and reliably generate organized multi-laminar tissues of multiple cell types at high
cell density. To date, no tissue engineering approach is capable of recreating multi-laminar polarized 3D
structures analogous to those that form at even the earliest stages in the embryo. Using our experience with
and expertise in embryonically assembled tissues, we leverage principles of the organizer, and engineer stable
multi-laminar tissues with planar polarity. Based on our published methods for shaping 3D embryonic tissues
into laminar sheets, we will to expose the cellular that stabilize those sheets and to develop assembly methods
to produce planar polarized tissues. Rapid translation to human biomedical research and tissue are made
possible by leveraging the speed and accessibility of the amphibian embryonic model to test and translate key
findings to human embryonic stem cell models of the organizer. We envision that the long term outcome of this
project will transform efforts to engineer and manufacture tissues that can be sourced from human cell types
and iPSCs for a wide range of clinical and research applications.
项目概要:
再生和发育在亚毫米尺度上进行,利用进化的设计原理
驱动替换器官和新器官的自组装。我们这个项目的目标是遵循以下原则
“组织者”,通过显微外科手术将一小群细胞移植到初始宿主组织中,以形成图案和
从幼稚组织诱导器官原基。为了实现这一目标,我们首先确定生产稳定的方法
原始组织(即稳定的宿主组织)的层状片,并开发新的工具来组装这些层状片
片材(即代替手动显微外科移植物)以形成平面偏振 3D 结构。这
推动现代组织工程的原理基于形态发生的经典胚胎学研究
在类器官中。这些经典研究依赖于两栖动物模型,可以从其中分离出特定的细胞
胚胎,形成聚集体,并分化成独特的组织。遵循排序和
通过吞噬和分化,细胞自组装具有不同极性的平面、极化层状片材,例如
从前到后,以高细胞密度形成由多种细胞类型组成的组织。现在已经广泛
认识到在胚胎发生过程中类似的、保守的自组装程序塑造了人体组织,
再生和癌症进展。然而,当前设计复杂 3D 结构的努力受到了以下问题的影响:
无法在高条件下可重复且可靠地生成多种细胞类型的有组织的多层组织
细胞密度。迄今为止,还没有组织工程方法能够重建多层偏振 3D
结构类似于胚胎最早阶段形成的结构。利用我们的经验
和胚胎组装组织方面的专业知识,我们利用组织者的原理,并设计稳定的
具有平面极性的多层组织。基于我们发布的 3D 胚胎组织塑造方法
成层状片材,我们将暴露稳定这些片材的细胞并开发组装方法
生产平面偏振组织。快速转化为人类生物医学研究和组织
通过利用两栖动物胚胎模型的速度和可访问性来测试和翻译关键
人类胚胎干细胞模型的组织者的研究结果。我们预计这一举措的长期结果
该项目将改变工程和制造可源自人类细胞类型的组织的努力
和 iPSC,用于广泛的临床和研究应用。
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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LANCE A. DAVIDSON其他文献
LANCE A. DAVIDSON的其他文献
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{{ truncateString('LANCE A. DAVIDSON', 18)}}的其他基金
Mechanical Control of Mesenchymal-to-Epithelial Transition
间充质到上皮转变的机械控制
- 批准号:
9336427 - 财政年份:2016
- 资助金额:
$ 22.59万 - 项目类别:
US National Symposium on Frontiers in Biomechanics: Mechanics of Development
美国国家生物力学前沿研讨会:发展力学
- 批准号:
8204038 - 财政年份:2011
- 资助金额:
$ 22.59万 - 项目类别:
Biophysics of development buffering: Temperature as a tool to study how the cytos
发育缓冲的生物物理学:温度作为研究细胞如何发育的工具
- 批准号:
7976887 - 财政年份:2010
- 资助金额:
$ 22.59万 - 项目类别:
Biophysics of development buffering: Temperature as a tool to study how the cytos
发育缓冲的生物物理学:温度作为研究细胞如何发育的工具
- 批准号:
8106442 - 财政年份:2010
- 资助金额:
$ 22.59万 - 项目类别:
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