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<p>Stress urinary incontinence (SUI) remains a significant clinical challenge due to the lack of strategies that simultaneously address muscle degeneration, neurogenic atrophy, and vascular deficits. Here, we report an innovative injectable system that combines a thermo-responsive poly(N-isopropylacrylamide)-COOH/leucine/decellularized extracellular matrix hydrogel with adipose-derived stem cells (ADSCs) pre-programmed by zeolitic imidazolate framework-8/polyethylene glycol 200@magnesium (ZIF-8/PEG200@Mg) nanoparticles. In vitro, programmed ADSCs exhibit enhanced neurogenic differentiation, while the hydrogels support robust myogenic activity and cell viability. In a female rat model of SUI—chosen to reflect the higher prevalence of SUI in women—the composite system leads to a marked improvement in leak point pressure (LPP) and restores urethral sphincter function. Mechanistic analyses reveals upregulation of muscle regeneration (e.g., <i>Myoz1</i>, <i>Smyd1</i>) and neurogenesis/neuromuscular junction stabilization (NMJ) stabilization genes (e.g., <i>Dok7</i>, <i>Musk</i>), highlighting a coordinated multi-lineage regenerative process. This work establishes an integrated regeneration-plus-support injectable strategy, offering a regenerative medicine-based approach that surpasses conventional bulking or sling therapies for SUI.</p>

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Injectable therapeutic system incorporating neurogenesis-programmed stem cells concomitantly promoting muscle regeneration treats stress urinary incontinence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月25日

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  • Wenzhuo Fang,
  • Xuan Du,
  • Ranxing Yang,
  • Meng Liu,
  • Ming Yang,
  • Yangwang Jin,
  • Guo Gao,
  • Qiang Fu,
  • Ying Wang

摘要

Stress urinary incontinence (SUI) remains a significant clinical challenge due to the lack of strategies that simultaneously address muscle degeneration, neurogenic atrophy, and vascular deficits. Here, we report an innovative injectable system that combines a thermo-responsive poly(N-isopropylacrylamide)-COOH/leucine/decellularized extracellular matrix hydrogel with adipose-derived stem cells (ADSCs) pre-programmed by zeolitic imidazolate framework-8/polyethylene glycol 200@magnesium (ZIF-8/PEG200@Mg) nanoparticles. In vitro, programmed ADSCs exhibit enhanced neurogenic differentiation, while the hydrogels support robust myogenic activity and cell viability. In a female rat model of SUI—chosen to reflect the higher prevalence of SUI in women—the composite system leads to a marked improvement in leak point pressure (LPP) and restores urethral sphincter function. Mechanistic analyses reveals upregulation of muscle regeneration (e.g., Myoz1, Smyd1) and neurogenesis/neuromuscular junction stabilization (NMJ) stabilization genes (e.g., Dok7, Musk), highlighting a coordinated multi-lineage regenerative process. This work establishes an integrated regeneration-plus-support injectable strategy, offering a regenerative medicine-based approach that surpasses conventional bulking or sling therapies for SUI.