Acta Medica Iranica 2017. 55(6):368-374.

Concomitant Transurethral and Transvaginal-Periurethral Injection of Autologous Adipose Derived Stem Cells for Treatment of Female Stress Urinary Incontinence: A Phase One Clinical Trial
Babak Arjmand, Majid Safavi, Reza Heidari, Hamidreza Aghayan, Soroush T. Bazargani, Sanaz Dehghani, Parisa Goodarzi, Fereshteh Mohammadi-Jahani, Fariba Heidari, Moloud Payab, Gholamreza Pourmand

Abstract


Stress urinary incontinence is a common medical problem among women. The urethral closure complex and/or the supportive mechanisms are responsible for incontinence in the majority of patients. Several surgical procedures with different degrees of invasiveness and outcomes have been reported to treat the problem. Although most of these procedures are reasonably effective, a general trend towards the study of natural and biocompatible tissues is emerging over popular synthetic materials. Here we report our experience of autologous adipose-derived stem cells transplantation into the periurethral region as a new method of stress urinary incontinence treatment. Ten women with symptoms of stress urinary incontinence were treated by injections of autologous adipose-derived stem cells into the periurethral region via transurethral and transvaginal approach under urethroscopic observation. This report presents the short-term outcome of the patients. The outcome measured by pad test results, ICIQ-SF scores, and Qmax. The mean age of the participants was 45.8±8.7 years. Urinary incontinence significantly decreased through the first two, 6 and 24 weeks after the injection therapy. The difference was significant in pad test results (P<0.001) and ICIQ-SF scores (P<0.001), especially comparing results between 2 and 6 weeks and among 6 and 24 weeks, but not for 2 and 6 weeks compared to each other. Surprisingly, Qmax showed improvement after the study period (means 32.6 vs. 35.7; P=0.002). This study showed that injection of the autologous adipose-derived stem cells to the periurethral region is a safe, yet short-term effective treatment option for stress urinary incontinence. Further studies with longer follow up are needed to confirm its long term efficacy.


Keywords


Urinary incontinence; Stress urinary incontinence; Stem cells; Adipose derived stem cell

Full Text:

PDF

References


Hu, T.W., et al., Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology, 2004. 63(3): p. 461-5.

Norton, P. and L. Brubaker, Urinary incontinence inwomen. Lancet, 2006. 367(9504): p. 57-67.

Gibbs, C.F., T.M. Johnson, 2nd, and J.G. Ouslander,Office management of geriatric urinary incontinence. AmJ Med, 2007. 120(3): p. 211-20.

Feldmann, H., [History of injections. Pictures from thehistory of otorhinolaryngology highlighted by exhibits ofthe German History of Medicine Museum in Ingolstadt].Laryngorhinootologie, 2000. 79(4): p. 239-46.

Herschorn, S., D.J. Steele, and S.B. Radomski, Followupof intraurethral collagen for female stress urinaryincontinence. J Urol, 1996. 156(4): p. 1305-9.

Politano, V.A., et al., Periurethral teflon injection forurinary incontinence. Trans Am Assoc Genitourin Surg,1973. 65: p. 54-7.7. Cervigni, M., et al., [Endoscopic treatment of sphincterinsufficiency with autologous fat injection]. Arch ItalUrol Androl, 1994. 66(4 Suppl): p. 219-24.

Kershen, R.T. and A. Atala, New advances in injectabletherapies for the treatment of incontinence andvesicoureteral reflux. Urol Clin North Am, 1999. 26(1): p.81-94.

Dmochowski, R.R. and R.A. Appell, Injectable agents in the treatment of stress urinary incontinence in women:where are we now? Urology, 2000. 56(6 Suppl 1): p. 32-40.

Sweat, S.D. and D.J. Lightner, Complications of sterileabscess formation and pulmonary embolism followingperiurethral bulking agents. J Urol, 1999. 161(1): p. 93-6.

Kerr, L.A., Bulking agents in the treatment of stressurinary incontinence: history, outcomes, patientpopulations, and reimbursement profile. Rev Urol, 2005.7(1): p. S3-S11.

Shamliyan, T.A., et al., Systematic review: randomized,controlled trials of nonsurgical treatments for urinaryincontinence in women. Ann Intern Med, 2008. 148(6): p.459-73.

Gilchrist, A.S. and E.S. Rovner, Managing complicationsof slings. Curr Opin Urol, 2011. 21(4): p. 291-6.

Winters, J.C. and R.A. Appell, Collagen injection therapyin the treatment of urinary incontinence. Tech Urol, 1996.2(2): p. 59-64.

Xu, Y., et al., Adipose-derived mesenchymal cells as apotential cell source for skeletal regeneration. Curr OpinMol Ther, 2005. 7(4): p. 300-5.

Safford, K.M., et al., Neurogenic differentiation of murineand human adipose-derived stromal cells. BiochemBiophys Res Commun, 2002. 294(2): p. 371-9.

Nagaya, N., et al., Transplantation of mesenchymal stemcells improves cardiac function in a rat model of dilatedcardiomyopathy. Circulation, 2005. 112(8): p. 1128-35.

Fraser, J.K., et al., Fat tissue: an underappreciated sourceof stem cells for biotechnology. Trends Biotechnol, 2006.24(4): p. 150-4.

Jiang, Y., et al., Pluripotency of mesenchymal stem cellsderived from adult marrow. Nature, 2002. 418(6893): p.1-9.

Dominici, M., et al., Minimal criteria for definingmultipotent mesenchymal stromal cells. The InternationalSociety for Cellular Therapy position statement.Cytotherapy, 2006. 8(4): p. 315-7.

Rehman, J., et al., Secretion of angiogenic andantiapoptotic factors by human adipose stromal cells.Circulation, 2004. 109(10): p. 1292-8.

Bacigalupo, A., et al., Bone marrow harvest for marrowtransplantation: effect of multiple small (2 ml) or large(20 ml) aspirates. Bone Marrow Transplant, 1992. 9(6): p.467-70.

Gluckman, E., et al., Bone marrow transplantation forsevere aplastic anemia: influence of conditioning andgraft-versus-host disease prophylaxis regimens onoutcome. Blood, 1992. 79(1): p. 269-75.

Zuk, P.A., et al., Human adipose tissue is a source ofmultipotent stem cells. Mol Biol Cell, 2002. 13(12): p.4279-95.

Zuk, P.A., et al., Multilineage cells from human adiposetissue: implications for cell-based therapies. Tissue Eng,2001. 7(2): p. 211-28.

Watanabe, T., et al, Increased urethral resistance byperiurethral injection of low serum cultured diposederivedmesenchymal stromal cells in rats. Int J Urol,2011. 18(9): p. 659-66.

Yamamoto, T., et al., Periurethral injection of autologousadipose-derived regenerative cells for the treatment ofmale stress urinary incontinence: Report of three initialcases. Int J Urol, 2012. 19(7): p. 652-9.

Mitterberger, M., et al., Adult stem cell therapy of femalestress urinary incontinence. Eur Urol, 2008. 53(1): p. 169-75.

Ishizuka, O., Editorial comment from Dr Ishizuka toperiurethral injection of autologous adipose-derivedregenerative cells for the treatment of male stress urinaryincontinence: report of three initial cases. Int J Urol. 2012Jul;19(7):659; author reply 659. doi: 10.1111/j.1442-2042.2012.03011.x. Epub 2012 Mar 27.

Wu, G., et al., Adipose-derived stromal celltransplantation for treatment of stress urinaryincontinence. Tissue Cell, 2011. 43(4): p. 246-53.31. Lin, G., et al., Treatment of stress urinary incontinencewith adipose tissue-derived stem cells.ytotherapy,2010. 12(1): p. 88-95.

Shirvan, M.K., et al., A novel cell therapy for stressurinary incontinence, short-term outcome. NeurourolUrodyn, 2013. 32(4): p. 377-82.

Kinebuchi, Y., et al., Autologous bone-marrow-derivedmesenchymal stem cell transplantation into injured raturethral sphincter. Int J Urol, 2010. 17(4): p. 359-68.

Garcia-Olmo, D., et al., A phase I clinical trial of thetreatment of Crohn's fistula by adipose mesenchymalstem cell transplantation. Dis Colon Rectum, 2005. 48(7):p. 1416-23.

Dai, R., et al., Adipose-Derived Stem Cells for TissueEngineering and Regenerative Medicine Applications.Stem Cells Int, 2016. 2016: p. 6737345.

Aref-Adib, M., et al., Stem cell therapy for stress urinaryincontinence: a systematic review in human subjects.Archives of gynecology and obstetrics, 2013. 288(6): p.1213-1221.

Zhou, S., et al., Stem cell therapy for treatment of StressUrinary Incontinence: the current status and challenges.Stem cells international, 2016. 2016.

Carr, L.K., et al., 1-year follow-up of autologous musclederivedstem cell injection pilot study to treat stressurinary incontinence. Int Urogynecol J Pelvic FloorDysfunct, 2008. 19(6): p. 881-3


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.