Advancing Fetal-Maternal Health: Microphysiological Models for Placental Development
Bibliographic record
Abstract
The placenta is a highly vascularized, temporary organ developed in pregnancy that is composed of both maternal and fetal cells. It plays a pivotal role in gestational health by facilitating embryo implantation and fostering nutrient exchange between mother and fetus. Placental malformation and the diffusion of harmful exogenous substances through the placental barrier can cause pregnancy complications and, in more severe cases, death of the mother or the fetus. Further, the placenta undergoes profound morphological and functional changes throughout pregnancy. Establishing models to mimic these phenomena at different stages of pregnancy informs prescription drug safety and expedites the development of placental disease treatments. Mouse models are often used to simulate human fetal development despite major interspecies differences. These limitations drive researchers to developing in vitro models consisting of human-derived cells. This thesis presents three 3D vascularized placental models utilizing human placental stem cells (PSCs) and human umbilical vein endothelial cells (HUVECs) which can model multiple placental phenomena across early- and late-stage pregnancy. The first model features a 3D fibrin hydrogel network with self-assembled vasculature and a monolayer of syncytialized human trophoblastic stem cells (STs) serving as a platform for barrier studies at the maternal-fetal interface. By tuning trophoblast differentiation and vascularization of this model to mimic the early- and late-stage placenta, it was revealed that placental barrier permeability was dependent on placental maturity and that the vascular barrier is also a critical determinant of what molecules can be passed from the mother to the fetus. The design and manufacturing of this model were then streamlined to meet the demands of large-scale drug studies in the second placental barrier model. Placental invasion into the maternal decidua is carefully orchestrated by multiple cell types to prevent over- and under-invasion, both of which can be dangerous to the mother and fetus. Understanding the biochemical and environmental cues that permit this healthy invasion can allow for improved diagnostics and treatments of placental diseases, such as preeclampsia and placenta accreta. Thus, the third model presented herein is a placental invasion model with chorionic villus-like structures seeded with invasive extravillous cytotrophoblasts (EVTs) and a perfusable vascular channel. Collectively, these models facilitate the exploration of placental morphogenesis and function throughout various stages of pregnancy. They offer a valuable tool for probing placental dysfunctions and assessing drug safety, ultimately contributing to advancements in fetal-maternal health.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".