Fig. 1: In vitro model of PAS recapitulates the abnormally deep trophoblastic invasion.
From: Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum
A Schematic showing abnormally deep invasion of extravillous trophoblasts (EVTs) in the decidual stroma proximal to scar. SCT: syncytiotrophoblast, CT: cytotrophoblast, dF: decidual fibroblast, Scar-dF: transformed dFs proximal to scar, Physio-dF: normal dFs distal to scar, V: placental villi, M: myometrium. B H&E and immunohistochemistry images of maternal-fetal interface tissue sections from PAS patients showing HLA-G+ EVT (green), and Vimentin labeled dFs (red); nuclei marked with DAPI (blue). n = 6 biological replicates. C Picrosirius red staining of tissue sections from regions proximal, and distal to pre-existent scar, with orientation distribution of collagen fibers from different PAS patients quantified in (D). n = 3 biological replicates. E Surface topography of Scar matrix imaged by atomic force microscopy (AFM) in PBS; F Photo and spatial rigidity characterization of normal endometrial tissue; Graph (bottom) shows mean rigidity of endometrial tissue, Physio, and Scar matrices. n = 8, 25, and 8 biologically independent experiments. p = 3 × 10−42. G Schematic showing workflow to establish in vitro Scar induced PAS model with distinct invasion assays. H, I Phase contrast image showing in-situ HTR8 spheroid invasion into ESFs decidualized on Physio; Graphs showing line integral convolution representation of HTR8 invasion into ESFs decidualized on Physio, or Scar matrices. I Normalized HTR8 invasion area (S/S0) as a function of invasion time. n = 10 biological replicates. J Fluorescent images of HTR8 (red) invasion into ESFs pre-decidualized on Physio, or Scar at time 0, and 24 h; Graph showing aerial invasion normalized to initial interface length; n = 8 interfaces; p = 0.005. K Apotome scanning of HTR8 spatial nuclear locations relative to dESF monolayers 72 h after invasion; L Quantification of individual HTR8 distance to dESF monolayer; n = 255 cells; p = 6 × 10−79. M Volcano plot showing differentially expressed genes in dESFs on Scar and Physio. N Ingenuity Pathway Analysis based prediction of activated transcription factors in dESFs on Scar and Physio; n = 3 biological replicates. Data in all bar graphs are showing as mean ± s.d.; statistical significance is determined by unpaired two-tailed t-test (**p < 0.01, ****p < 0.0001, and ns not significant). Source data are provided as a Source Data file. A, G created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en).
