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

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  • Wenzhuo Fang

    (Shanghai Jiao Tong University)

  • Xuan Du

    (Shanghai Jiao Tong University)

  • Ranxing Yang

    (Shanghai Jiao Tong University)

  • Meng Liu

    (Shanghai Jiao Tong University)

  • Ming Yang

    (Shanghai Jiao Tong University)

  • Yangwang Jin

    (Shanghai Jiao Tong University)

  • Guo Gao

    (Shanghai Jiao Tong University)

  • Qiang Fu

    (Shanghai Jiao Tong University)

  • Ying Wang

    (Shanghai Jiao Tong University)

Abstract

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.

Suggested Citation

  • Wenzhuo Fang & Xuan Du & Ranxing Yang & Meng Liu & Ming Yang & Yangwang Jin & Guo Gao & Qiang Fu & Ying Wang, 2025. "Injectable therapeutic system incorporating neurogenesis-programmed stem cells concomitantly promoting muscle regeneration treats stress urinary incontinence," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63421-2
    DOI: 10.1038/s41467-025-63421-2
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