Modeling human trophoblast-NK cell interactions in term and preterm birth
足月和早产时人类滋养层 - NK 细胞相互作用的建模
基本信息
- 批准号:10770207
- 负责人:
- 金额:$ 15.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Administrative SupplementAlloantigenAnimal ModelBasal PlateBiological ModelsBlood flowCell CommunicationCell Differentiation processCell ReprogrammingCellsDataDeciduaDecidual CellEndometriumEnvironmentEpithelial CellsFaceFemaleFetusFirst Pregnancy TrimesterFlow CytometryFunctional disorderGenerationsGoalsGrantGrowth and Development functionHumanImmuneImmune responseImmunofluorescence ImmunologicInflammatoryInnate Immune ResponseInvadedKnowledgeLeukocytesMaternal-Fetal ExchangeMesenchymal Stem CellsMethodsModelingNatural Killer CellsPatientsPeripheral Blood Mononuclear CellPhenotypePlacentaPlacentationPopulationPregnancyPregnant UterusPremature BirthPremature LaborProcessPublishingRegenerative MedicineReproducibilityResolutionResourcesRiskSendai virusSeriesSex DifferencesStagingStudy modelsSurfaceTechnologyTissuesUmbilical cord structureUterusVascular remodelingVillousWorkadaptive immune responseamnioncell bankcell typeexperiencefetalhuman modelhuman pluripotent stem cellin vitro Modelin vivoinduced pluripotent stem cellinsightmalematernal immune systempathogenprogramsresponsesexsingle-cell RNA sequencingtranscriptomicstrophoblastvascular abnormality
项目摘要
Project Summary/Abstract
The human placenta is a semi-allogeneic tissue whose growth and development requires tolerance by the
maternal immune system. In fact, the maternal immune system faces a challenge during pregnancy: to
maintain tolerance toward foreign fetal alloantigens while simultaneously staging a response to potential
pathogens at the maternal-fetal interface. The mechanisms through which placental cells evade maternal
immune recognition are poorly understood, particularly in the context of human pregnancy. The uterine
lining, called decidua, is a particularly-understudied and important microenvironment, because it is the
interface where placental cells called extravillous trophoblast (EVT) come in close contact with maternal
immune cells, of which decidual natural killer (dNK) cells are the most abundant. EVT are highly invasive
cells which are required for proper remodeling of the maternal uterine lining, including vascular
remodeling which leads to establishment of maternal blood flow to the placenta. Interactions between
placental EVT and decidual leukocytes are known to facilitate maternal vascular remodeling by EVT and
limit the extent of EVT invasion into the uterine wall. Indeed, problems in preterm birth could result from
inappropriate responses by dNK cells. Unfortunately, interactions between dNK and trophoblasts are
difficult to study in an ongoing pregnancy, due to lack of access to the decidual compartment, where these
important interactions occur. While animal models have offered some insights into these processes, they
do not accurately model human placentation and pregnancy. The goal of the original R01 proposal is to
evaluate the decidual cell population in both term and preterm birth, then to combine this knowledge with
the latest technologies in regenerative medicine to develop in vitro models for the study of dNK-EVT
interactions. Specifically, we proposed to generate matched maternal and placental induced pluripotent
stem cells (iPSC), and differentiate these cells into dNK cells and EVT, respectively, in order to model
interactions between these two cell types. Given the known association between male fetal sex and risk of
preterm birth, we had focused our efforts on characterizing, banking, and reprogramming cells from
mom:male baby pairs in the original application. However, to fully understand mechanisms that
predispose to sPTB, it would be best to compare these data to those from mom:female baby pairs.
Therefore, we now propose to characterize, bank, and reprogram cells from mom:female placenta
pairs for this administrative supplement. Successful completion of this proposal will establish a
reproducible and manipulatable model system for studying interactions between the maternal immune
system and both the male and female placenta.
项目总结/文摘
项目成果
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{{ truncateString('Jack D Bui', 18)}}的其他基金
Modeling human trophoblast-NK cell interactions in term and preterm birth
足月和早产时人类滋养层 - NK 细胞相互作用的建模
- 批准号:
10211100 - 财政年份:2021
- 资助金额:
$ 15.8万 - 项目类别:
Modeling human trophoblast-NK cell interactions in term and preterm birth
足月和早产时人类滋养层 - NK 细胞相互作用的建模
- 批准号:
10549321 - 财政年份:2021
- 资助金额:
$ 15.8万 - 项目类别:
Modeling human trophoblast-NK cell interactions in term and preterm birth
足月和早产时人类滋养层 - NK 细胞相互作用的建模
- 批准号:
10370386 - 财政年份:2021
- 资助金额:
$ 15.8万 - 项目类别:
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