한빛사 논문
Kwonwoo Song a,1, Ahmed Abdal Dayem a,1, Soobin Lee a, Yujin Choi a, Kyung Min Lim a, Sehee Kim a, Jongyub An a, Yeokyung Shin a, Hyojin Park a, Tak-Il Jeon a, Soo Bin Jang a, Hanbit Bong a, Jeong Ik Lee c, Geun-Ho Kang d, Sejong Kim d, Aram Kim b,*, Ssang-Goo Cho a,*
a Department of Stem Cell & Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea b Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05029, Republic of Korea c Department of Veterinary Obstetrics and Theriogenology, College of Veterinary Medicine, and Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Seoul 05029, Republic of Korea d R&D Team, StemExOne Co., Ltd., 303, Life Science Bldg, 120, Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
* Corresponding authors.
1 These authors contributed equally to this work.
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.
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