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<p>Diabetes mellitus (DM) is characterized by the loss or dysfunction pancreatic β-cells. Human amniotic epithelial cells (hAEC), which retain pluripotency markers and are readily obtainable from term placentas, represent a promising alternative source of stem cells. We investigated whether hAECs can be guided through pancreatic ontogeny to generate insulin-producing β-like cells. hAEC from uncomplicated term deliveries were expanded to passage&#xa0;1 and exposed to a four-stage&#xa0;differentiation sequence that sequentially modulated Activin/WNT, KGF/TGF-β, retinoic-acid/hedgehog, and EGF/Noggin signaling. Stage progression was monitored by end-point RT-PCR and quantitative immunofluorescence for hallmark transcription factors. After definitive endoderm induction, 64% of cells were Brachyury positive and 71% were WNT3A positive; primitive-gut specification yielded 57% HNF1B<sup>+</sup> cells. Posterior foregut commitment produced 75% PDX1<sup>+</sup> and 60% Sox9<sup>+</sup> nuclei and the final endocrine stage&#xa0;generated 74% NKX2.2<sup>+</sup> cells, with 71% showing cytoplasmatic insulin and 51% C-peptide staining; insulin/C-peptide co-localization was confirmed by double labelling. Thus a chemically defined, four-step protocol can convert term-derived hAEC into insulin-producing β-like cells, supporting their use as an accessible platform for diabetes modelling and future cell-replacement therapies.</p>

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Differentiation to insulin-positive cells from human amnion epithelial cells using a pancreatic development mimicry protocol

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月14日

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  • Daniel Martínez-Rodríguez,
  • Jonathan Salazar-Alonso,
  • Axel Castro-Abrego,
  • Daniela Ávila-González,
  • Omar Martínez-Alarcón,
  • Anayansi Molina-Hernández,
  • Alejandro Martínez-Juárez,
  • Héctor Salvador Godoy-Morales,
  • Diana Elizabeth Lara-Barragán,
  • Wendy Portillo,
  • Nestor Emmanuel Díaz-Martínez,
  • Guadalupe García-López,
  • Nestor Fabián Díaz

摘要

Diabetes mellitus (DM) is characterized by the loss or dysfunction pancreatic β-cells. Human amniotic epithelial cells (hAEC), which retain pluripotency markers and are readily obtainable from term placentas, represent a promising alternative source of stem cells. We investigated whether hAECs can be guided through pancreatic ontogeny to generate insulin-producing β-like cells. hAEC from uncomplicated term deliveries were expanded to passage 1 and exposed to a four-stage differentiation sequence that sequentially modulated Activin/WNT, KGF/TGF-β, retinoic-acid/hedgehog, and EGF/Noggin signaling. Stage progression was monitored by end-point RT-PCR and quantitative immunofluorescence for hallmark transcription factors. After definitive endoderm induction, 64% of cells were Brachyury positive and 71% were WNT3A positive; primitive-gut specification yielded 57% HNF1B+ cells. Posterior foregut commitment produced 75% PDX1+ and 60% Sox9+ nuclei and the final endocrine stage generated 74% NKX2.2+ cells, with 71% showing cytoplasmatic insulin and 51% C-peptide staining; insulin/C-peptide co-localization was confirmed by double labelling. Thus a chemically defined, four-step protocol can convert term-derived hAEC into insulin-producing β-like cells, supporting their use as an accessible platform for diabetes modelling and future cell-replacement therapies.