title: The potential role of stem cells in the treatment of urinary incontinence.
abstract: Voiding dysfunction encompasses a wide range of urologic disorders including stress urinary incontinence and overactive bladder that have a detrimental impact on the quality of life of millions of men and women worldwide. In recent years, we have greatly expanded our understanding of the pathophysiology of these clinical conditions. However, current gold standard therapies often provide symptomatic relief without targeting the underlying etiology of disease development. Recently, the use of stem cells to halt disease progression and reverse underlying pathology has emerged as a promising method to restore normal voiding function. Stem cells are classically thought to aid in tissue repair via their ability for multilineage differentiation and self-renewal. They may also exert a therapeutic effect via the secretion of bioactive factors that direct other stem and progenitor cells to the area of injury, and that also possess antiapoptotic, antiscarring, neovascularization, and immunomodulatory properties. Local injections of mesenchymal, muscle-derived, and adipose-derived stem cells have all yielded successful outcomes in animal models of mechanical, nerve, or external urethral sphincter injury in stress urinary incontinence. Similarly, direct injection of mesenchymal and adipose-derived stem cells into the bladder in animal models of bladder overactivity have demonstrated efficacy. Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects. Although many challenges remain to be addressed prior to the clinical implementation of this technology, novel stem-cell-based therapies are an exciting potential therapy for voiding dysfunction.
authors: Glickman Urological and Kidney Institute, The Cleveland Clinic, USA.
authors: Christine
authors: C
authors: Tran
authors: The Cleveland Clinic, Department of Biomedical Engineering, 9500 Euclid Avenue ND20, Cleveland, OH 44195, USA.
authors: Margot S
authors: MS
authors: Damaser
keywords: mechanism of action; mesenchymal stem cells; overactive bladder; regenerative medicine; secretome; systemic therapy; tissue engineering; urinary incontinence
references: Cell Res. 2013 Jan;23(1):33-48
references: 23277278
references: Stem Cells Int. 2013;2013:130763
references: 24194766
references: Stem Cells. 2013 Sep;31(9):1840-56
references: 23666768
references: PLoS One. 2010 Feb 24;5(2):e9357
references: 20195358
references: Exp Hematol. 2002 Jan;30(1):42-8
references: 11823036
references: Br J Haematol. 2013 Nov;163(4):501-9
references: 23992039
references: BJU Int. 2010 May;105(9):1276-82
references: 19912188
references: Stem Cells Dev. 2012 Jun 10;21(9):1391-400
references: 22008016
references: Cell Stem Cell. 2012 Mar 2;10(3):244-58
references: 22385653
references: Diabet Med. 2012 Jan;29(1):14-23
references: 21883442
references: Kidney Int. 2002 Feb;61(2):387-95
references: 11849378
references: Circ Res. 2008 Nov 21;103(11):1204-19
references: 19028920
references: Biomed Res Int. 2013;2013:930713
references: 24151627
references: World J Urol. 2003 May;20(6):327-36
references: 12811491
references: Ther Clin Risk Manag. 2013;9:161-70
references: 23637536
references: Biomaterials. 2013 Nov;34(34):8617-29
references: 23932297
references: Int J Mol Med. 2012 Mar;29(3):416-22
references: 22109789
references: Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1888-97
references: 19395555
references: Stem Cells Dev. 2009 Jun;18(5):683-92
references: 19099374
references: J Urol. 2008 Aug;180(2):753-9
references: 18554634
references: J Urol. 2009 Dec;182(6 Suppl):S18-26
references: 19846137
references: J Cell Biochem. 2006 Aug 1;98(5):1076-84
references: 16619257
references: Urol Int. 2011;86(1):110-6
references: 20689260
references: Int J Urol. 2013 Jan;20(1):116-22
references: 23126506
references: Surg Endosc. 2009 Apr;23(4):765-8
references: 18622542
references: Haematologica. 2007 Apr;92(4):440-9
references: 17488654
references: J Urol. 2011 Aug;186(2):640-7
references: 21683398
references: J Inflamm (Lond). 2005 Jul 26;2:8
references: 16045800
references: PLoS One. 2013;8(1):e53980
references: 23349776
references: Science. 1998 Nov 6;282(5391):1145-7
references: 9804556
references: J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86
references: 19958962
references: Urology. 2003 Oct;62(4 Suppl 1):39-44
references: 14550836
references: Exp Hematol. 2000 Aug;28(8):875-84
references: 10989188
references: Cytotherapy. 2010;12(1):88-95
references: 19878076
references: J Urol. 2003 Jan;169(1):237-9
references: 12478144
references: Rejuvenation Res. 2010 Aug;13(4):429-38
references: 20583954
references: Neurourol Urodyn. 2007;26(7):966-71
references: 17580339
references: Cell Transplant. 2014;23(11):1395-406
references: 23866688
references: Nat Rev Urol. 2012 Aug;9(8):435-47
references: 22710667
references: Int J Urol. 2014 Mar;21(3):294-300
references: 24033774
references: Obstet Gynecol Int. 2012;2012:612946
references: 21941558
references: Int Urogynecol J Pelvic Floor Dysfunct. 2008 Jun;19(6):881-3
references: 18204978
references: J Urol. 2012 Jun;187(6):2087-92
references: 22498227
references: J Am Heart Assoc. 2013 Oct 10;2(5):e000338
references: 24113326
references: J Korean Med Sci. 2010 May;25(5):663-70
references: 20436699
references: J Urol. 2005 Nov;174(5):2041-5
references: 16217390
references: Blood. 2003 Aug 15;102(4):1548-9
references: 12900350
references: Stem Cell Res. 2011 May;6(3):206-14
references: 21419744
references: Int Urogynecol J. 2011 Sep;22(9):1075-83
references: 21505907
references: Tissue Eng Part A. 2011 Aug;17(15-16):2123-32
references: 21513463
references: Am J Physiol Renal Physiol. 2005 Jul;289(1):F31-42
references: 15713913
references: Cell. 2006 Aug 25;126(4):663-76
references: 16904174
references: Can Urol Assoc J. 2013 Sep;7(9-10 Suppl 4):S186-8
references: 24523841
references: Stem Cells. 2006 Apr;24(4):1030-41
references: 16253981
references: Urology. 1998 Jul;52(1):143-51
references: 9671889
references: J Urol. 2011 Mar;185(3):1132-8
references: 21255803
references: Cell. 2001 May 4;105(3):369-77
references: 11348593
references: Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1278-90
references: 17071732
references: Ann Biomed Eng. 2004 Oct;32(10):1409-19
references: 15535058
references: PLoS One. 2011;6(10):e26535
references: 22046303
references: Methods Mol Biol. 2013;1037:27-43
references: 24029928
references: J Investig Dermatol Symp Proc. 2003 Jun;8(1):28-38
references: 12894992
references: Gene Ther. 2009 Apr;16(4):533-46
references: 19129861
references: Transplantation. 2010 May 15;89(9):1043-9
references: 20150836
references: J Urol. 2010 Mar;183(3):1232-40
references: 20096880
references: Stem Cells. 2008 Jul;26(7):1787-95
references: 18499892
references: Curr Stem Cell Res Ther. 2011 Sep;6(3):221-8
references: 21476975
references: BJU Int. 2004 Feb;93(3):324-30
references: 14764130
references: Eur Urol. 2009 Feb;55(2):322-33
references: 18963418
references: Rev Urol. 2004;6 Suppl 3:S3-9
references: 16985863
references: Lancet. 2003 Aug 30;362(9385):697-703
references: 12957092
references: Transplant Proc. 2013 Mar;45(2):503-10
references: 23498785
references: Circ Cardiovasc Genet. 2012 Feb 1;5(1):o8-o18
references: 22337932
references: Blood. 2006 Dec 1;108(12):3938-44
references: 16896152
references: Neurourol Urodyn. 2012 Mar;31(3):386-9
references: 22431263
references: J Urol. 2013 Apr;189(4):1588-94
references: 23022009
references: Cell Transplant. 2012;21(8):1641-50
references: 22506988
references: World J Urol. 1997;15(5):268-74
references: 9372577
references: Urology. 2010 Mar;75(3):718-23
references: 19969332
references: Biomaterials. 2010 Jun;31(18):4872-9
references: 20303586
references: Biomaterials. 2013 Jan;34(4):1311-26
references: 23137393
references: Obstet Gynecol. 2004 Sep;104(3):607-20
references: 15339776
references: BJU Int. 2008 Sep;102(7):774-9
references: 18616691
references: Neurourol Urodyn. 2004;23(2):166-71
references: 14983430
references: Br J Obstet Gynaecol. 1997 Sep;104(9):988-93
references: 9307522
references: Methods Mol Biol. 2013;1001:65-80
references: 23494421
references: Pediatr Surg Int. 2010 Jan;26(1):79-84
references: 19855985
references: Cell Transplant. 2011;20(1):5-14
references: 21396235
references: Am J Physiol Renal Physiol. 2012 Nov 1;303(9):F1363-9
references: 22993071
references: J Cell Mol Med. 2007 Jan-Feb;11(1):21-38
references: 17367499
references: Urology. 2004 Apr;63(4):780-5
references: 15072911
references: Science. 1999 Apr 2;284(5411):143-7
references: 10102814
references: J Crohns Colitis. 2008 Jun;2(2):99-106
references: 21172199
references: Leukemia. 2003 Jan;17(1):160-70
references: 12529674
references: J Urol. 2009 Jan;181(1):397-400
references: 19010492
references: Exp Hematol. 1974;2(2):83-92
references: 4455512
references: J Natl Cancer Inst. 2004 Sep 15;96(18):1358-67
references: 15367568
references: JAMA. 2012 Dec 12;308(22):2369-79
references: 23117550
references: Biomaterials. 2012 Jun;33(16):4031-43
references: 22421386
references: J Urol. 2008 Nov;180(5):2226-33
references: 18804817
references: J Urol. 2013 Feb;189(2):595-601
references: 23260547
references: Handb Exp Pharmacol. 2011;(202):45-67
references: 21290221
references: J Urol. 2007 Apr;177(4):1568-72
references: 17382780
references: Blood. 2004 Nov 1;104(9):2643-5
references: 15251986
references: Urology. 2000 Jan;55(1):58-61
references: 10654895
references: Cell Transplant. 2012;21(5):959-70
references: 22449414
references: Cell Transplant. 2008;17(3):303-11
references: 18522233
references: Cell Transplant. 2015;24(6):1043-52
references: 24593859
references: Eur Urol. 2004 Jul;46(1):15-27
references: 15183544
references: Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634-8
references: 6950406
references: Neurourol Urodyn. 2000;19(1):53-69
references: 10602248