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Superior therapeutic activity of TGF-β-induced extracellular vesicles against interstitial cystitis
Kwonwoo Song1, Ahmed Abdal Dayem1, Soobin Lee1
1Department of Stem Cell & Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
Abstract:
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by incapacitating pelvic pain. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered key mediators of the paracrine action of MSCs and show better biological activities than the parent MSCs, especially in the bladder tissue, which may be unfavorable for MSC survival. Here, we produced MSC-EVs using advanced three-dimensional (a3D) culture with exogenous transforming growth factor-β3 (TGF-β3) (T-a3D-EVs). Treatment with T-a3D-EVs led to significantly enhanced wound healing and anti-inflammatory capacities. Moreover, submucosal layer injection of T-a3D-EVs in chronic IC/BPS animal model resulted in restoration of bladder function, superior anti-inflammatory activity, and recovery of damaged urothelium compared to MSCs. Interestingly, we detected increased TGF-β1 level in T-a3D-EVs, which might be involved in the anti-inflammatory activity of these EVs. Taken together, we demonstrate the excellent immune-modulatory and regenerative abilities of T-a3D-EVs as observed by recovery from urothelial denudation and dysfunction, which could be a promising therapeutic strategy for IC/BPS.
Insights
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) modified with TGF-β3 show enhanced therapeutic potential for interstitial cystitis/bladder pain syndrome (IC/BPS). These T-a3D-EVs promote bladder healing and reduce inflammation, offering a promising treatment strategy.
Area of Science:
- Regenerative Medicine
- Urology
- Cell Biology
Background:
- Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing severe pelvic pain.
- Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer therapeutic benefits, potentially overcoming limitations of parent mesenchymal stem cells (MSCs) in bladder tissue.
- MSC-EVs are key mediators of MSC paracrine action.
Purpose of the Study:
- To investigate the therapeutic potential of advanced three-dimensional (a3D) culture-derived MSC-EVs modified with transforming growth factor-β3 (TGF-β3) for treating IC/BPS.
- To evaluate the efficacy of these modified EVs (T-a3D-EVs) in promoting bladder repair and reducing inflammation in an IC/BPS animal model.
Main Methods:
- Production of MSC-EVs using advanced three-dimensional (a3D) culture with exogenous TGF-β3.
- Assessment of T-a3D-EVs' wound healing and anti-inflammatory capacities in vitro.
- Submucosal injection of T-a3D-EVs into a chronic IC/BPS animal model.
- Evaluation of bladder function, inflammation, and urothelial recovery post-treatment.
Main Results:
- T-a3D-EVs demonstrated significantly enhanced wound healing and anti-inflammatory properties compared to unmodified MSC-EVs.
- Submucosal injection of T-a3D-EVs restored bladder function and promoted urothelial recovery in the IC/BPS model.
- T-a3D-EVs exhibited superior anti-inflammatory activity and urothelial regeneration compared to MSCs in vivo.
- Increased TGF-β1 levels were detected in T-a3D-EVs, potentially contributing to their anti-inflammatory effects.
Conclusions:
- T-a3D-EVs possess potent immune-modulatory and regenerative capabilities beneficial for IC/BPS.
- These modified EVs facilitate recovery from urothelial damage and dysfunction.
- T-a3D-EVs represent a promising cell-free therapeutic strategy for interstitial cystitis/bladder pain syndrome.
