Use of bioactive extracellular matrix fragments as a urethral bulking agent to treat stress urinary incontinence

Ying Wang; Meng Duan; Mahbubur Rahman; Ming Yang; Weixin Zhao; Shukui Zhou; Guo Gao; Qiang Fu

doi:10.1016/j.actbio.2020.09.049

Use of bioactive extracellular matrix fragments as a urethral bulking agent to treat stress urinary incontinence

Acta Biomater. 2020 Nov:117:156-166. doi: 10.1016/j.actbio.2020.09.049. Epub 2020 Oct 6.

Authors

Ying Wang¹, Meng Duan², Mahbubur Rahman³, Ming Yang¹, Weixin Zhao⁴, Shukui Zhou⁵, Guo Gao⁶, Qiang Fu⁷

Affiliations

¹ Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai 200233, China.
² Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
³ Department of General Educational Development, Faculty of Science and Information Technology, Daffodil International University, Dhaka 1207, Bangladesh.
⁴ Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine Winston-Salem, NC 27157, USA.
⁵ Department of Urology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China. Electronic address: 2005507098@163.com.
⁶ Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: guogao@sjtu.edu.cn.
⁷ Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai 200233, China. Electronic address: jamesqfu@aliyun.com.

PMID: 33035698
DOI: 10.1016/j.actbio.2020.09.049

Abstract

Injection of urethral bulking agents is a low-risk, minimally invasive surgical procedure to treat stress urinary incontinence (SUI). In this study, we developed a promising injectable bulking agent comprising extracellular matrix fragments of adipose-derived stem cell sheets (ADSC ECM) and investigated its effectiveness in urethral bulking therapy. The structural integrity and proteins of ADSC sheet ECM were well retained in decellularized ADSC ECM fragments. To locate transplanted ADSC ECM fragments, they were labeled with ultrasmall super-paramagnetic iron oxide nanoparticles, which enabled in vivo monitoring after implantation in a SUI rat model for up to 4 weeks. When ADSC ECM fragments were injected into the rat urethra, they became fully integrated with the surrounding tissue within 1 week. Four weeks after transplantation, host cells had regenerated within the ADSC ECM fragment injection area. Moreover, new smooth muscle tissue had formed around the ADSC ECM fragments, as confirmed by positive staining of myosin. These results indicate that injection of ECM fragments may be a promising minimally invasive approach for treating SUI.

Keywords: Adipose-derived stem cells; Decellularization; Extracellular matrix; Stress urinary incontinence; Tissue engineering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Animals
Extracellular Matrix
Male
Rats
Stem Cells
Urethra
Urinary Incontinence, Stress* / therapy