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

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

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63421-2

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