Engineering a biomimetic matrix to promote development of human ovarian follicles in vitro
工程仿生基质促进人类卵泡体外发育
基本信息
- 批准号:10311304
- 负责人:
- 金额:$ 4.05万
- 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:2021-08-19 至 2024-08-18
- 项目状态:已结题
- 来源:
- 关键词:AgeAngiopoietinsApoptoticAtlasesAutologous TransplantationAutomobile DrivingBasement membraneBioinformaticsBiologicalBiomimeticsCaliberCancer SurvivorCell ProliferationCellsCharacteristicsChemistryClinicClinicalComplexComputational BiologyCortex of ovaryCoupledCryopreservationData SetDepositionDevelopmentDissociationEmbryoEndocrineEngineeringEnvironmentExtracellular MatrixExtracellular Matrix ProteinsFertilityFertilizationFlow CytometryFluorescenceFutureGene Expression ProfileGene Expression ProfilingGerm CellsGoalsGrowthGrowth FactorHormonalHormone ResponsiveHormonesHumanHydrogelsIn VitroIndividualInfertilityKnowledgeLifeLigand BindingMalignant NeoplasmsMechanicsMethodsMolecular BiologyMusNatureOocytesOvarianOvarian FollicleOvarian TissueOvarian tissue cryopreservationOvaryPGF geneParacrine CommunicationPathway interactionsPatientsPeptide HydrolasesPeptidesPlatelet-Derived Growth FactorPopulationPregnancyPrimordial FollicleProceduresProtocols documentationReproducibilityResearchRiskRoleSavingsSignal TransductionSomatic CellSorting - Cell MovementStainsStandardizationStimulusStromal CellsStructureSupplementationSupport SystemSuspensionsSystemTissue EngineeringTranslatingTranslationsVascular Endothelial Growth FactorsWomanWorkagedangiogenesisanticancer treatmentautocrinebasecancer cellcancer recurrencecancer riskcancer therapycomparativecytokinecytotoxicdesigneggethylene glycolfertility improvementfertility preservationfolliculogenesisgirlshuman tissueimprovedin vivoinnovationnext generation sequencingnoveloocyte cryopreservationoocyte retrievalparacrineprepubertyprimary ovarian insufficiencyprospectivereproductivescaffoldself assemblysingle cell sequencingsingle-cell RNA sequencingstandard of caresuccessthree dimensional structuretissue culturetranscription factortranscriptometranscriptomics
项目摘要
The long-term goal of the proposed research is to establish a broad fertility preservation option for women undergoing gonadotoxic anticancer treatments and facing infertility. The overall objective of this proposal in working towards the presented goal and mitigating the risks associated with autotransplantation is to create a biomimetic environment that promotes human follicle development from the primordial stage in vitro. The low success rates of small follicle culture are largely attributed to the complex and poorly understood paracrine, autocrine and endocrine signaling between follicular cells, neighboring follicles, and stromal cells. The central hypothesis is that transcriptional profiling of human follicles will reveal mechanisms driving development and recreating the ovarian microenvironment through design of a biomimetic hydrogel which retains cell-secreted extracellular matrix (ECM) will support human follicle development in vitro. The rationale for the proposed work is that by deciphering the mechanisms driving follicle activation and early development, and recapitulating the natural ovarian microenvironment in an ECM-sequestering hydrogel, future culture systems can be translated to the clinic for maturation of cryopreserved ovarian follicles and subsequent fertilization and pregnancy. In the first aim, single cell RNA sequencing will be used to profile human ovarian follicles and supportive stromal cells. In the second aim, ECM-sequestering peptides will be incorporated in a biomimetic poly (ethylene glycol) (PEG) hydrogel system using Michael-type addition chemistry to promote deposition of ECM components and mimic the native ovarian tissue. The follicle’s basement membrane is composed of ECM proteins and it functions as structural support for follicular cells, a selective barrier for molecules entering the follicle, and a scaffold for retaining soluble growth factors and cytokines. It is continuously remodeled during follicle development, but cell- secreted ECM molecules are unable to adhere to unmodified PEG for self-assembly. By integrating ECM- sequestering peptides in the PEG hydrogels, the structural and biological roles of ECM can be restored for in vitro follicle development. The contribution of this work will be a single cell atlas of the reproductive-age ovary highlighting mechanisms driving follicle development and stromal cells’ supportive roles in folliculogenesis and a novel in vitro follicle culture system that supports human follicle development. The contribution of this work will be significant because it will guide the development of a standardized in vitro culture for maturation of human follicles and a safe fertility preservation option for patients unable to produce mature eggs as a result of gonadotoxic treatments. The proposed work is innovative in that it will be the first single cell dataset from healthy reproductive aged women and the first instance of human follicle culture in a synthetic ECM-sequestering matrix.
拟议研究的长期目标是为接受性腺毒性抗癌治疗并面临不孕症的女性建立广泛的生育力保留选择。该提案致力于实现所提出的目标并减轻与自体移植相关的风险,其总体目标是创建一个仿生环境,促进人类卵泡从体外原始阶段发育。小卵泡培养的低成功率很大程度上归因于卵泡细胞、邻近卵泡和基质细胞之间复杂且知之甚少的旁分泌、自分泌和内分泌信号传导。中心假设是,人类卵泡的转录谱将揭示驱动发育的机制,并通过设计保留细胞分泌的细胞外基质(ECM)的仿生水凝胶来重建卵巢微环境,从而支持人类卵泡的体外发育。这项工作的基本原理是,通过破译驱动卵泡激活和早期发育的机制,并在 ECM 隔离水凝胶中重现自然卵巢微环境,未来的培养系统可以应用于临床,用于冷冻保存的卵泡的成熟以及随后的受精和妊娠。第一个目标是利用单细胞 RNA 测序来分析人类卵泡和支持性基质细胞。第二个目标是,利用迈克尔型加成化学将 ECM 螯合肽纳入仿生聚乙二醇 (PEG) 水凝胶系统中,以促进 ECM 成分的沉积并模拟天然卵巢组织。毛囊的基底膜由 ECM 蛋白组成,其功能是毛囊细胞的结构支撑、分子进入毛囊的选择性屏障以及保留可溶性生长因子和细胞因子的支架。它在卵泡发育过程中不断重塑,但细胞分泌的 ECM 分子无法粘附到未修饰的 PEG 上进行自组装。通过将 ECM 螯合肽整合到 PEG 水凝胶中,可以恢复 ECM 的结构和生物学作用,以促进体外卵泡发育。这项工作的贡献将是育龄卵巢的单细胞图谱,突出显示驱动卵泡发育的机制和基质细胞在卵泡发生中的支持作用,以及支持人类卵泡发育的新型体外卵泡培养系统。这项工作的贡献将是巨大的,因为它将指导人类卵泡成熟的标准化体外培养物的开发,并为因性腺毒性治疗而无法产生成熟卵子的患者提供安全的生育力保存选择。这项工作的创新之处在于,它将是第一个来自健康生育年龄女性的单细胞数据集,也是第一个在合成 ECM 隔离基质中进行人类卵泡培养的实例。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Andrea Jones其他文献
Andrea Jones的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Andrea Jones', 18)}}的其他基金
Engineering a biomimetic matrix to promote development of human ovarian follicles in vitro
工程仿生基质促进人类卵泡体外发育
- 批准号:
10671614 - 财政年份:2021
- 资助金额:
$ 4.05万 - 项目类别:
相似国自然基金
益肺清化颗粒对血管生成因子及VEGF/KDR和Angiopoietins /Tie2信号传导通路的调控作用研究
- 批准号:30973841
- 批准年份:2009
- 资助金额:32.0 万元
- 项目类别:面上项目
相似海外基金
Evaluation of Angiopoietins as Prognostic Markers of Kidney Allograft Structure and Function
血管生成素作为肾同种异体移植结构和功能的预后标志物的评价
- 批准号:
10301502 - 财政年份:2021
- 资助金额:
$ 4.05万 - 项目类别:
Evaluation of Angiopoietins as Prognostic Markers of Kidney Allograft Structure and Function
血管生成素作为肾同种异体移植结构和功能的预后标志物的评价
- 批准号:
10487563 - 财政年份:2021
- 资助金额:
$ 4.05万 - 项目类别:
Evaluation of Angiopoietins as Prognostic Markers of Kidney Allograft Structure and Function
血管生成素作为肾同种异体移植结构和功能的预后标志物的评价
- 批准号:
10626144 - 财政年份:2021
- 资助金额:
$ 4.05万 - 项目类别:
Differential agonistic activities of angiopoietins on neutrophils
血管生成素对中性粒细胞的差异激动活性
- 批准号:
304873 - 财政年份:2014
- 资助金额:
$ 4.05万 - 项目类别:
Operating Grants
The Role of Angiopoietins 1 and 2 in ANCA Associated Vasculitis
血管生成素 1 和 2 在 ANCA 相关性血管炎中的作用
- 批准号:
MR/K000977/1 - 财政年份:2013
- 资助金额:
$ 4.05万 - 项目类别:
Fellowship
Expression and functional roles of angiopoietins in lymphangiogenesis and development of lymphatic induction system
血管生成素在淋巴管生成和淋巴诱导系统发育中的表达和功能作用
- 批准号:
21590217 - 财政年份:2009
- 资助金额:
$ 4.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Agonistic activities of angiopoietins on neutrophils
血管生成素对中性粒细胞的激动活性
- 批准号:
181135 - 财政年份:2009
- 资助金额:
$ 4.05万 - 项目类别:
Operating Grants
Elucidation of molecular mechanisms of angiogenesis mediated by angiopoietins and its application for asthma therapy
阐明血管生成素介导的血管生成的分子机制及其在哮喘治疗中的应用
- 批准号:
20590901 - 财政年份:2008
- 资助金额:
$ 4.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Regulation of skeletal muscle injury and regeneration by angiopoietins
血管生成素对骨骼肌损伤和再生的调节
- 批准号:
171081 - 财政年份:2008
- 资助金额:
$ 4.05万 - 项目类别:
Operating Grants
The Role of Tie2 and the Angiopoietins in EPC Biology
Tie2 和血管生成素在 EPC 生物学中的作用
- 批准号:
6999609 - 财政年份:2005
- 资助金额:
$ 4.05万 - 项目类别:














{{item.name}}会员




