000041313 001__ 41313 000041313 005__ 20240125142332.0 000041313 0247_ $$2doi$$a10.6083/bpxhc41313 000041313 037__ $$aIR 000041313 041__ $$aeng 000041313 245__ $$aDevelopment of a 3-dimensional trophoblast organoid model system 000041313 260__ $$bOregon Health and Science University 000041313 269__ $$a2023-07-20 000041313 336__ $$aAbstract 000041313 520__ $$aAccess to early gestational placental tissue in humans is constrained by a host of ethical challenges. As a result, early events of placentation and fetal development are poorly understood. The need for superior modelling capabilities has sparked interest in tissue-derived organoids in a translational animal model. Using tissue derived from rhesus macaque (Macaca mulatta) as a model system is favorable due to their structural and developmental similarities to the human placenta, and their ability to alleviate ethical concerns. Organoids are 3-dimensional cell cultures that assemble into miniature versions of their parent tissue. This makes them an invaluable tool for in vitro studies. Placental organoids can be generated by collecting proliferative cytotrophoblast cells from early gestational timepoints. These cells retain their stemness and can organize into organoids expressing cytotrophoblast (CTB) and syncytiotrophoblast (SYN) cell types. Crucially, placental organoids can be induced to differentiate into extravillous trophoblast (EVT), which are the cell phenotype responsible for anchoring the placenta to the maternal decidua. One caveat of trophoblast organoids is the inversion between their SYN and CTB cell layers. As the maternal/fetal blood barrier, SYN reside outside CTB in normal placentae, whereas in organoids they are found in the innermost layers. SYN are responsible for oxygen, nutrient, and waste exchange between the mother and fetus. Proper exterior presentation of SYN will allow manipulation of in vitro conditions and facilitate effective functional studies. Developing trophoblast organoid models from the Rhesus macaque which are meticulously characterized and validated will be important for discovery and innovation. Correcting polarity alongside characterization will offer an incredibly powerful tool for researchers to examine questions around early placental development, as well as assaying what external stimuli (e.g., drugs, virus) can cross or impact the function of the maternal/fetal barrier, and yield insight into the mechanisms of placentation and maternal blood supply.  000041313 540__ $$fCC BY 000041313 542__ $$fIn copyright - single owner 000041313 650__ $$aDevelopmental Biology$$028463 000041313 650__ $$aNutrients$$012949 000041313 650__ $$aFetal Blood$$018985 000041313 650__ $$aCell Culture Techniques, Three Dimensional$$013579 000041313 650__ $$aMacaca mulatta$$021724 000041313 650__ $$aPlacenta$$024210 000041313 650__ $$aFemale$$018941 000041313 650__ $$aPregnancy$$024523 000041313 650__ $$aOrganoids$$023278 000041313 650__ $$aTrophoblasts$$027422 000041313 650__ $$aHumans$$020376 000041313 650__ $$aFetal Development$$035918 000041313 6531_ $$areproductive biology 000041313 6531_ $$aplacental tissue 000041313 6531_ $$aplacental organoids 000041313 692__ $$aDivision of Reproductive & Developmental Sciences$$041468 000041313 692__ $$aOregon National Primate Research Center$$041497 000041313 7001_ $$aWessel, Brady$$uOregon Health and Science University$$041354 000041313 711__ $$aResearch Week$$uOregon Health and Science University$$d2023 000041313 7201_ $$aRoberts, Victoria$$uOregon Health & Science University$$7Personal 000041313 8564_ $$9ce2e54da-a252-43b8-b4b4-4631ed8ef799$$s165508$$uhttps://digitalcollections.ohsu.edu/record/41313/files/ResearchWeek.2023.Wessel.Brady.pdf 000041313 980__ $$aResearch Week 000041313 981__ $$aPublished$$b2023-07-20