The Human Placenta Project

Basic Research Premeeting Discussion Summary - L Myatt & Y Sadovsky

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Key Achievements/Breakthroughs

• Development of trophoblast and decidual organoids

• Induced pluripotent stem cells

• Introduction of single cell and spatial technology to probe placental biology

• Appreciation of the roles of extracellular vesicles and the development of tools to probe their mechanism of action and function

• Advances in "omics" technologies and integration of "omic" data

• Emergence of microfluidic multicellular systems to capture villus biology

• Appreciation of sexual dimorphism in placental biology/function

Gaps in Knowledge

• Deeper insights into pre-pregnancy, pre-implantation and blastocyst biology and early placental development

• Immune interactions at the placenta-decidual interface

• A lack of broad high dimensional placental data sets across gestation, similar to the Cancer Atlas

• The impact of race/ethnicity/age/socioeconomic status/environment on placental development and function

• Tools to predict long term impact on child and adult health and wellness

Challenges

• Histopathology standards are not sensitive enough to delineate disease pathogenesis and differentiate clinical entities, particularly considering tissue availability only upon delivery

• Integration of placental biology, imaging and epidemiology and deep phenotyping of gestational health

• Deployment of complex and expensive imaging modalities to define placental function across pregnancy

• Organoids remain technically cumbersome and not widely accessible

• The knowledge in the extracellular vesicles landscape has not been deep enough for proper definitions of vesicle types, action, and regulation

• Inadequately standardized protocols for tissue collection and storage with flexibility to adapt to needs of emerging technologies

• A lack of agreed upon standardized data dictionaries for collection and recording of clinical data to facilitate comparison and data aggregation

• Engagement and interaction of basic scientists, bioinformaticians, engineers, and other disciplines into study of the placenta

• The translation of basic mechanisms to diagnostics, therapeutics, disease prevention

Opportunities

• Bolster the field of placental histopathology with molecular diagnostics

• Further the success of organoid cultures including establishing accessible organoids that capture the maternal-fetal interface across all three trimesters

• Refine the use of iPSC to build models and study trophoblast biology and interactions with other villous and extravillous cell types

• Study and define basic placental immunology and its relationship to successful establishment of pregnancy and to adverse outcomes

• Integration of omics and clinical data to advance knowledge on trajectories of a healthy pregnancy, and shed insight on problems even prior to clinical manifestations

• Utilize artificial intelligence and machine learning approaches to build phenotypes that link placental development and function across pregnancy

• Develop and utilize cutting edge tools for the use of animal models, such as guinea pig, marmoset monkey

• Collection and phenotyping of placentas that represent rare biology or pathology and comparison of extreme phenotypes, and making them accessible to all researchers

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