{
  "id": 16502868,
  "title": "Mechanical history shapes phenotypic plasticity and fibroblast-autonomous 3D remodeling in iPSC-derived cardiac fibroblasts",
  "url": "https://urgent.news/2026/10/25/mechanical-history-shapes-phenotypic-plasticity-and-fibroblast",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-10-25T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.20.759862v1?rss=1"
  },
  "original_language": "en",
  "account": "Human induced pluripotent stem cell-derived cardiac fibroblasts (iPSC-cFBs) provide a renewable and genetically defined source for studying cardiac fibrosis and fibroblast-cells interaction during development and disease. While iPSC-cFBs are proliferative and suitable for applications like drug screening and tissue engineering, expansion in culture can lead to a premature change from fibroblasts to myofibroblasts. This study explores how the differentiation protocol, mechanical culture history, and serial expansion affect iPSC-cFB phenotype, transforming growth factor beta 1 (TGF-beta1) sensitivity, and fibroblast-autonomous remodeling in three-dimensional (3D) tissues.\n\nStudies on iPSC-cFBs expanded on conventional tissue-culture polystyrene (TCP) showed an increase in cell area and alpha-smooth muscle actin (alpha-SMA) expression over time. These markers are linked to fibroblast-to-myofibroblast transition (FMT). The researchers then investigated how the stiffness of poly(dimethylsiloxane) (PDMS) substrates (15 kPa or 2 MPa) during derivation and expansion impacted the basal phenotype and response to TGF-beta1. Across two independent differentiation methods, the mechanical culture history affected the passage-dependent basal characteristics and TGF-beta1 responses.\n\nInterestingly, the mechanical culture history's influence on collective TGF-beta1 responses in 3D cultures differed from the effects seen when cells were replated on two-dimensional substrates. In summary, these results indicate that mechanical culture history modulates the responsiveness and tissue-remodeling behavior of iPSC-cFBs without permanently determining their fibroblast state. Following more passages and varying microenvironments can either diminish or re-establish these history-dependent features. This research supports the application of iPSC-cFBs in both basic biological discoveries and potential tissue engineering advancements.",
  "summary": "Human induced pluripotent stem cell-derived cardiac fibroblasts (iPSC-cFBs) offer a renewable, genetically defined stromal cell source for studying cardiac fibrosis and cardiomyocyte-fibroblast crosstalk during development and disease. Because cardiac fibroblasts are proliferative, expansion of iPSC-cFBs in culture is attractive for applications requiring large cell numbers, including drug…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}