Yonsei Med J.  2016 Sep;57(5):1152-1158. 10.3349/ymj.2016.57.5.1152.

Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study

Affiliations
  • 1Department of Urology, College of Medicine, Yeungnam University, Daegu, Korea.
  • 2Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea. tgkwon@knu.ac.kr
  • 3Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
  • 4Department of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.
  • 5Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Korea.

Abstract

PURPOSE
We report our initial experience with transurethral injection of autologous adipose-derived regenerative cells (ADRCs) for the treatment of urinary incontinence after radical prostatectomy.
MATERIALS AND METHODS
After providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up.
RESULTS
Urine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H2O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up.
CONCLUSION
This study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence.

Keyword

Urinary incontinence; injections; adipose tissue; regenerative medicine

MeSH Terms

Adipose Tissue/*cytology/transplantation
Aged
Female
Humans
Injections/methods
Magnetic Resonance Imaging
Male
Middle Aged
Prostatectomy/*adverse effects
Quality of Life
Stem Cell Transplantation/*methods
Surveys and Questionnaires
Transplantation, Autologous
Treatment Outcome
Urethra/diagnostic imaging
Urinary Incontinence/etiology/*therapy

Figure

  • Fig. 1 Before injection, the external urethral sphincter was open. Solution and adipose tissue was injected into the rhabdosphincter and submucosal space at the 5 and 7 o'clock positions and at the 4, 6, and 8 o'clock positions to facilitate complete coaptation of the urethral mucosa by the bulking effect.

  • Fig. 2 In case of patient E, MRI showed an increase in the functional urethral length (from 5.07 to 8.59 mm) between the lower rim of the pubic bone and bladder neck 4 weeks after injection (A: baseline, B: 4 wks after injection).

  • Fig. 3 Changes in 24-h pad test, MUCP, MRI, ICIQ-SF. MUCP, maximum urethral closing pressure; MRI, magnetic resonance imaging; ICIQ-SF, International Consultation on Incontinence Questionnaire-Short Form.


Reference

1. Bauer RM, Bastian PJ, Gozzi C, Stief CG. Postprostatectomy incontinence: all about diagnosis and management. Eur Urol. 2009; 55:322–333.
Article
2. Clemens JQ, Schuster TG, Konnak JW, McGuire EJ, Faerber GJ. Revision rate after artificial urinary sphincter implantation for incontinence after radical prostatectomy: actuarial analysis. J Urol. 2001; 166:1372–1375.
Article
3. Giberti C, Gallo F, Schenone M, Cortese P, Ninotta G. Stem cell therapy for male urinary incontinence. Urol Int. 2013; 90:249–252.
Article
4. Kinebuchi Y, Aizawa N, Imamura T, Ishizuka O, Igawa Y, Nishizawa O. Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincter. Int J Urol. 2010; 17:359–368.
Article
5. Zhao W, Zhang C, Jin C, Zhang Z, Kong D, Xu W, et al. Periurethral injection of autologous adipose-derived stem cells with controlled-release nerve growth factor for the treatment of stress urinary incontinence in a rat model. Eur Urol. 2011; 59:155–163.
Article
6. Roche R, Festy F, Fritel X. Stem cells for stress urinary incontinence: the adipose promise. J Cell Mol Med. 2010; 14:135–142.
Article
7. Zeng X, Jack GS, Zhang R. Treatment of SUI using adipose derived stem cells: restoration of urethral function. J Urol. 2006; 175:291.
Article
8. Zhang Y, Luo H, Zhang Z, Lu Y, Huang X, Yang L, et al. A nerve graft constructed with xenogeneic acellular nerve matrix and autologous adipose-derived mesenchymal stem cells. Biomaterials. 2010; 31:5312–5324.
Article
9. Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM, et al. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 2010; 12:88–95.
Article
10. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004; 109:1292–1298.
Article
11. Gotoh M, Yamamoto T, Kato M, Majima T, Toriyama K, Kamei Y, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients. Int J Urol. 2014; 21:294–300.
Article
12. Lin K, Matsubara Y, Masuda Y, Togashi K, Ohno T, Tamura T, et al. Characterization of adipose tissue-derived cells isolated with the Celution system. Cytotherapy. 2008; 10:417–426.
Article
13. Strasser H, Marksteiner R, Margreiter E, Mitterberger M, Pinggera GM, Frauscher F, et al. Transurethral ultrasonography-guided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence. World J Urol. 2007; 25:385–392.
Article
14. Strasser H, Marksteiner R, Margreiter E, Pinggera GM, Mitterberger M, Frauscher F, et al. Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial. Lancet. 2007; 369:2179–2186.
Article
15. Mitterberger M, Marksteiner R, Margreiter E, Pinggera GM, Frauscher F, Ulmer H, et al. Myoblast and fibroblast therapy for post-prostatectomy urinary incontinence: 1-year followup of 63 patients. J Urol. 2008; 179:226–231.
Article
16. Gerullis H, Eimer C, Georgas E, Homburger M, El-Baz AG, Wishahi M, et al. Muscle-derived cells for treatment of iatrogenic sphincter damage and urinary incontinence in men. ScientificWorldJournal. 2012; 2012:898535.
Article
17. García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005; 48:1416–1423.
Article
18. Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci U S A. 2002; 99:8932–8937.
Article
19. Yoshimura K, Matsumoto D, Gonda K. A clinical trial of soft-tissue augmentation by lipoinjection with adipose-derived stromal cells (ASC). In : International Fat Applied Technology Society (IFATS); Third Annual Meeting; 2005. p. 9–10.
20. Rangappa S, Fen C, Lee EH, Bongso A, Sim EK. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg. 2003; 75:775–779.
Article
21. Watanabe T, Maruyama S, Yamamoto T, Kamo I, Yasuda K, Saka Y, et al. Increased urethral resistance by periurethral injection of low serum cultured adipose-derived mesenchymal stromal cells in rats. Int J Urol. 2011; 18:659–666.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr