The Mesenchymal Component of Human Amniotic Membrane Drives Wound Healing



The Mesenchymal Component of Human Amniotic Membrane Drives Wound Healing

Summary: This study dissects the therapeutic roles of epithelial (hAEC) and mesenchymal stromal cells (hAMSC) in human amniotic membrane (hAM) for wound healing, using a chronified keratinocyte model (SSTC-HaCaT) to mimic diabetic foot ulcers. Conditioned media from hAMSC significantly enhanced migration (via c-Jun/ERK pathway), cytoskeletal remodeling (F-actin/paxillin), proliferation (G1 rescue), and gene modulation (down IL6/CDKNs, up CCNA2) compared to hAEC or intact hAM. hAMSC’s potency persisted across passages, confirming its primary contribution to hAM’s efficacy in chronic wounds, with implications for scalable cell-based therapies to overcome stalled healing.

Key Highlights:

  • hAMSC-CM boosted keratinocyte migration in scratch assays, stronger than hAEC-CM or hAM, via c-Jun overexpression at wound edges.
  • Cytoskeletal effects: hAMSC-CM induced focal adhesions and F-actin reorganization for motility in both serum-starved and TGF-β chronified models.
  • Proliferation rescue: Reduced G1 arrest in SSTC-HaCaT cells, with hAMSC-CM restoring cell cycle more effectively than hAEC-CM.
  • Gene expression: Downregulated inflammatory/arrest genes (IL6, CDKN2B, CDKN1A) and upregulated CCNA2, mimicking hAM’s anti-chronic effects.
  • Relevance: hAMSC as key driver for DFU therapies; supports targeted mesenchymal components for clinical translation.

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    Keywords: human amniotic membrane, hAMSC, chronic wound model, c-Jun pathway, keratinocyte migration