Releasing, activating, and maturing follicles from cortical tissue utilizing dynamic synthetic microenvironment
利用动态合成微环境释放、激活和成熟皮质组织中的毛囊
基本信息
- 批准号:10710212
- 负责人:
- 金额:$ 23.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-26 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-Dimensional3D PrintAddressArchitectureAssisted Reproductive TechnologyAutologous TransplantationBiocompatible MaterialsBiologicalBioprosthesis deviceCancer PatientCattleCell AggregationCellsChildClinicControlled EnvironmentCryopreservationCryopreserved TissueCuesDevelopmentDiseaseEffectivenessEmbryo TransferEmbryonic DevelopmentEngineeringEnvironmentFertilityFertilizationFertilization in VitroFoundationsFreezingFutureGelatinGenderGoalsGraafian FolliclesGrowing FollicleGrowthHumanHydrogelsIn SituIn VitroIndividualInfertilityInfusion proceduresLeftLive BirthMechanicsMethodsModelingMusOocytesOvarianOvarian FollicleOvarian TissueOvarian tissue cryopreservationOvaryOvulationPatientsPorosityPrimordial FollicleProceduresProcessProductionPropertyProtocols documentationReportingResearchResearch PersonnelRiskSecondary toStromal CellsStructureSupporting CellTechniquesTechnologyTestingTimeTissuesVariantWorkbioscaffoldcell motilitychildhood cancer survivordensitydesigneggfertility preservationfolliculogenesishuman tissueimprovedin vivomigrationnovel strategiesoffspringoocyte maturationoocyte qualityovary transplantationpatient populationrestorationsuccesstissue culturetooltransmasculineuterine receptivityzygote
项目摘要
PROJECT SUMMARY/ABSTRACT
Ovarian tissue cryopreservation (OTC), a fertility preservation option for cancer patients and others at increased
risk of developing infertility that is ideally performed prior to the gonadotoxic treatment, has enabled >140 live
births. However, fertility restoration is currently limited to transplantation of OTC tissue, and some patients may
not be able to use this option due to the risk of reintroducing their disease. An alternative that is not yet developed
for the clinic, would be to use the primordial follicles, the oocyte and support cell units that are cryopreserved in
OTC, and perform in vitro growth and maturation (IVGM) to produce eggs. Current assisted reproductive
technologies require 20 – 30 eggs to offer a good chance of producing a child. However, current IVGM protocols
performed in the research lab are not efficient and yield only a few eggs for every 10 or more patients.
Importantly, the success of current methods for isolating primordial follicles from ovarian tissue drastically differs
between patients and, at best, only a small percentage are obtained intact. Secondary follicles more easily
remain intact, but few are cryopreserved during OTC. Therefore, primordial follicles must be activated to grow to
secondary follicles if OTC tissue is used to make eggs. The rate limiting steps for advancing IVGM are: (1)
efficiently and reliably isolating healthy primordial follicles that are activated to grow, and (2) efficiently and
reliably growing and maturing secondary follicles into good quality eggs. 3D-printed bioscaffolds of specific
architectures can support the viability and growth of secondary follicles through egg maturation in vitro, as well
as primordial follicle growth and maturation through egg maturation, ovulation, and live birth in mice. These
promising results lay the foundation to further explore the use of specifically designed bioscaffolds to address
current limitations of IVGM. This application tests the hypothesis that a dynamic synthetic microenvironment will
provide the necessary mechanical and architectural cues to induce stromal cell migration out of ovarian tissue,
release of the embedded follicles, and support follicle growth and oocyte maturation into an egg. 3D-printed
bioscaffolds of varying mechanical and remodeling properties using tunable highly porous biomaterials will be
utilized to induce follicle migration from cortical tissue and provide a dynamic environment that remodels over
time as the follicles grow. Bovine ovaries as used to mimic human ovaries in size, cortical density, follicle growth
and maturation for the following aims: (1) to define the bioscaffolds that support stromal cell migration and
subsequent release, activation, and growth of primordial follicles; and (2) to define the bioscaffolds that induce
growth and maturation of isolated secondary follicles in vitro. These studies will identify specific properties of
synthetic microenvironments that can enhance follicle isolation from ovarian tissue, as well as those that support
the growth and maturation of follicles into eggs. If successful, this work would enable researchers to study
folliculogenesis from primordial follicle activation to an egg in a controlled environment, would uncover a
completely novel approach to IVGM and support the development of future technologies for IVGM in humans.
项目总结/摘要
卵巢组织冷冻保存(OTC)是癌症患者和其他增加生育能力的患者的生育能力保存选择。
理想情况下,在性腺毒性治疗之前进行不孕症的风险,已使>140人的生活
出生然而,生育力恢复目前仅限于OTC组织移植,一些患者可能
不能使用这个选项,因为有重新引入疾病的风险。尚未开发的替代品
对于临床来说,将使用冷冻保存的原始卵泡,卵母细胞和支持细胞单位,
OTC,并进行体外生长和成熟(IVGM)以产生卵子。当前辅助生殖
技术需要20 - 30个卵子才能提供生育孩子的良好机会。然而,目前的IVGM方案
在研究实验室进行的卵子移植效率不高,每10个或更多的病人只能得到几个卵子。
重要的是,目前从卵巢组织中分离原始卵泡的方法的成功与否
在患者之间,最好的情况下,只有一小部分是完整的。次级卵泡更容易
保持完整,但在OTC期间很少冷冻保存。因此,原始卵泡必须被激活才能生长,
次级卵泡,如果OTC组织用于产卵。推进IVGM的限速步骤是:(1)
有效且可靠地分离被激活生长的健康原始卵泡,和(2)有效且
次级卵泡可靠地生长和成熟为优质卵子。3D打印的生物支架
结构可以支持次级卵泡的活力和生长,通过卵子体外成熟,以及
如原始卵泡的生长和成熟,通过卵子成熟、排卵和小鼠的活产。这些
有希望的结果奠定了基础,以进一步探索使用专门设计的生物支架,以解决
IVGM的局限性。这个应用程序测试了一个假设,即一个动态的合成微环境将
提供必要的机械和结构线索以诱导基质细胞迁移出卵巢组织,
释放嵌入的卵泡,并支持卵泡生长和卵母细胞成熟为卵子。3D打印
使用可调的高度多孔的生物材料,
用于诱导毛囊从皮质组织迁移,并提供动态环境,
随着卵泡的生长。牛卵巢在大小、皮质密度、卵泡生长等方面模拟人类卵巢
(1)确定支持基质细胞迁移的生物支架,
随后的原始卵泡的释放、激活和生长;以及(2)确定诱导原始卵泡生长的生物支架。
体外分离的次级卵泡的生长和成熟。这些研究将确定的具体性质,
合成微环境,可以增强卵泡分离卵巢组织,以及那些支持
卵泡发育成熟为卵子。如果成功,这项工作将使研究人员能够研究
在受控环境中,从原始卵泡激活到卵子的卵泡发生,将揭示
这是IVGM的一种全新方法,并支持人类IVGM未来技术的发展。
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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Monica M Laronda其他文献
Recreating the female reproductive tract in vitro using iPSC technology in a linked microfluidics environment
- DOI:
10.1186/scrt374 - 发表时间:
2013-12-01 - 期刊:
- 影响因子:7.300
- 作者:
Monica M Laronda;Joanna E Burdette;J Julie Kim;Teresa K Woodruff - 通讯作者:
Teresa K Woodruff
Monica M Laronda的其他文献
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{{ truncateString('Monica M Laronda', 18)}}的其他基金
Organizing and Reorganizing Human Testis Development In Vitro
体外组织和重组人类睾丸发育
- 批准号:
10817412 - 财政年份:2023
- 资助金额:
$ 23.02万 - 项目类别:
Reverse Engineering the Extracellular Neighborhood to Support the Functional Tissue Unit: A Use Case to Restore Ovarian Function
对细胞外邻域进行逆向工程以支持功能组织单位:恢复卵巢功能的用例
- 批准号:
10530993 - 财政年份:2022
- 资助金额:
$ 23.02万 - 项目类别:
Admin. Supplement for Reverse Engineering the Extracellular Neighborhood to Support the Functional Tissue Unit: A Use Case to Restore Ovarian Function
行政。
- 批准号:
10814646 - 财政年份:2022
- 资助金额:
$ 23.02万 - 项目类别:
Releasing, activating, and maturing follicles from cortical tissue utilizing dynamic synthetic microenvironment
利用动态合成微环境释放、激活和成熟皮质组织中的毛囊
- 批准号:
10593624 - 财政年份:2022
- 资助金额:
$ 23.02万 - 项目类别:
Reverse Engineering the Extracellular Neighborhood to Support the Functional Tissue Unit: A Use Case to Restore Ovarian Function
对细胞外邻域进行逆向工程以支持功能组织单位:恢复卵巢功能的用例
- 批准号:
10689815 - 财政年份:2022
- 资助金额:
$ 23.02万 - 项目类别:
Defining the microenvironment that will enable a long-term bioprosthetic ovary transplant
定义可实现长期生物假体卵巢移植的微环境
- 批准号:
10617189 - 财政年份:2021
- 资助金额:
$ 23.02万 - 项目类别:
Defining the microenvironment that will enable a long-term bioprosthetic ovary transplant
定义可实现长期生物假体卵巢移植的微环境
- 批准号:
10180721 - 财政年份:2021
- 资助金额:
$ 23.02万 - 项目类别:
Defining the microenvironment that will enable a long-term bioprosthetic ovary transplant
定义可实现长期生物假体卵巢移植的微环境
- 批准号:
10394956 - 财政年份:2021
- 资助金额:
$ 23.02万 - 项目类别:
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