Tzu Chi Medical Journal
Volume 20, Issue 3 , Pages 169-176, September 2008

Regenerative Therapy for Stress Urinary Incontinence

  • Ron Jankowski

      Affiliations

    • Cook MyoSite, Inc., Pittsburgh, PA, USA
    • ,
  • Ryan Pruchnic

      Affiliations

    • Cook MyoSite, Inc., Pittsburgh, PA, USA
    • ,
  • David Wagner

      Affiliations

    • Cook MyoSite, Inc., Pittsburgh, PA, USA
    • ,
  • Michael B. Chancellor

      Affiliations

    • Department of Urology, William Beaumont Hospital, Royal Oak, MI, USA
    • Corresponding Author InformationCorresponding author. Department of Urology, William Beaumont Hospital, 438 Medical Office Building, 3535 West 13 Mile Road, Royal Oak, MI 48073, USA

Received 2 January 2008; received in revised form 29 January 2008; accepted 1 February 2008.

Article Outline

Abstract 

In anatomical and functional studies of the human and animal urethra, the middle urethral contained rhabdosphincter is critical for maintaining continence. Transplanted muscle and/or stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. Cell-based therapies include the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as muscle-derived stem cells and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. We will review the neurophysiology of stress urinary incontinence (highlighting the importance of the middle urethra); current injectable cell sources for cystoscopic treatment; and the potential of muscle-derived cells.

Keywords:  Adipose , Muscle , Stem cells , Urethral sphincter , Urinary incontinence

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References 

  1. Corcos J , Beaulieu S , Donovan J , et al.   Quality of life assessment in men and women with urinary incontinence . J Urol . 2002;168:896–905
  2. Norton P , Brubaker L . Urinary incontinence in women . Lancet . 2006;367:57–67
  3. Hampel C , Wienhold D , Benken N , Eggersmann C , Thuroff JW . Prevalence and natural history of female incontinence . Eur Urol . 1997;32(Suppl 2):3–12
  4. Bump RC , Norton PA . Epidemiology and natural history of pelvic floor dysfunction . Obstet Gynecol Clin North Am . 1998;25:723–746
  5. Peschers U , Schaer G , Anthuber C , Delancey JO , Schuessler B . Changes in vesical neck mobility following vaginal delivery . Obstet Gynecol . 1996;88:1001–1006
  6. Thom DH , van den Eeden SK , Brown JS . Evaluation of parturition and other reproductive variables as risk factors for urinary incontinence in later life . Obstet Gynecol . 1997;90:983–989
  7. Meyer S , Schreyer A , De Grandi P , Hohlfeld P . The effects of birth on urinary continence mechanisms and other pelvicfloor characteristics . Obstet Gynecol . 1998;92:613–618
  8. Sampselle CM , Miller JM , Mims BL , Delancey JO , Ashton-Miller JA , Antonakos CL . Effect of pelvic muscle exercise on transient incontinence during pregnancy and after birth . Obstet Gynecol . 1998;91:406–412
  9. McGuire EJ , Lytton B , Pepe V , Kohorn EI . Stress urinary incontinence . Obstet Gynecol . 1976;47:255–264
  10. Blaivas JG . A modest proposal for the diagnosis and treatment of urinary incontinence in women . J Urol . 1987;138:597–598
  11. Kayigil O , Iftekhar Ahmed S , Metin A . The coexistence of intrinsic sphincter deficiency with type II stress incontinence . J Urol . 1999;162:1365–1366
  12. Radley SC , Chapple CR , Bryan NP , Clarke DE , Craig DA . Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebocontrolled, doubleblind crossover study . Neurourol Urodyn . 2001;20:43–52
  13. Chancellor MB . Duloxetine for treatment of stress urinary incontinence . Evid Based OBGYN . 2004;6:196
  14. Herschorn S , Glazer AA . Early experience with small volume periurethral polytetrafluoroethylene for female stress urinary incontinence . J Urol . 2000;163:1838–1842
  15. Sakamoto K , Sharma S , Wheeler JS . Long-term subjective continence status and use of alternative treatments by women with stress urinary incontinence after collagen injection therapy . World J Urol . 2007;25:431–433
  16. Maher CF , O'Reilly BA , Dwyer PL , Carey MP , Cornish A , Schluter P . Pubovaginal sling versus transurethral macroplastique for stress urinary incontinence and intrinsic sphincter deficiency: a prospective randomised controlled trial . BJOG . 2005;112:797–801
  17. Chrouser KL , Fick F , Goel A , Itano NB , Sweat SD , Lightner DJ . Carbon coated zirconium beads in betaglucan gel and bovine glutaraldehyde crosslinked collagen injections for intrinsic sphincter deficiency: continence and satisfaction after extended followup . J Urol . 2004;171:1152–1155
  18. Bent AE , Tutrone RT , McLennan MT , Lloyd LK , Kennelly MJ , Badlani G . Treatment of intrinsic sphincter deficiency using autologous ear chondrocytes as a bulking agent . Neurourol Urodyn . 2001;20:157–165
  19. Sweat SD , Lightner DJ . Complications of sterile abscess formation and pulmonary embolism following periurethral bulking agents . J Urol . 1999;161:93–96
  20. McKinney CD , Gaffey MJ , Gillenwater JY . Bladder outlet obstruction after multiple periurethral polytetrafluoroethylene injections . J Urol . 1995;153:149–151
  21. Papa Petros PE . Tissue reaction to implanted foreign materials for cure of stress incontinence . Am J Obstet Gynecol . 1994;171:1159
  22. Kiilholma PJ , Chancellor MB , Makinen J , Hirsch IH , Klemi PJ . Complications of Teflon injection for stress urinary incontinence . Neurourol Urodyn . 1993;12:131–137
  23. Lee JY , Cannon TW , Pruchnic R , Fraser MO , Huard J , Chancellor MB . The effects of periurethral musclederived stem cell injection on leak point pressure in a rat model of stress urinary incontinence . Int Urogynecol J Pelvic Floor Dysfunct . 2003;14:31–37
  24. Edwards RG . A burgeoning science of embryological genetics demands a modern ethics . Reprod Biomed Online . 2007;15(Suppl 1):34–40
  25. DeLancey JO . Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis . Am J Obstet Gynecol . 1994;170:1713–1723
  26. Schroder HD , Reske-Nielsen E . Fiber types in the striated urethral and anal sphincters . Acta Neuropathol . 1983;60:278–282
  27. De Groat WC . Integrative control of the lower urinary tract: preclinical perspective . Br J Pharmacol . 2006;147(Suppl 2):S25–S40
  28. Chancellor MB , Perkin H , Yoshimura N . Recent advances in the neurophysiology of stress urinary incontinence . Scand J Urol Nephrol . 2005;39:21–24
  29. Thor KB , Katofiasc MA . Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloraloseanesthetized female cat . J Pharmacol Exp Ther . 1995;274:1014–1024
  30. Kaiho Y , Kamo I , Chancellor MB , Arai Y , de Groat WC , Yoshimura N . Role of noradrenergic pathways in sneezeinduced urethral continence reflex in rats . Am J Physiol Renal Physiol . 2007;292:F639–F646
  31. Kamo I , Torimoto K , Chancellor MB , de Groat WC , Yoshimura N . Urethral closure mechanisms under sneezeinduced stress condition in rats: a new animal model for evaluation of stress urinary incontinence . Am J Physiol Regul Integr Comp Physiol . 2003;285:R356–R365
  32. Kamo I , Kaiho Y , Canon TW , et al.   Functional analysis of active urethral closure mechanisms under sneeze induced stress condition in a rat model of birth trauma . J Urol . 2006;176:2711–2715
  33. De Groat WC . Anatomy of the central neural pathways controlling the lower urinary tract . Eur Urol . 1998;34(Suppl 1):2–5
  34. Kamo I , Cannon TW , Conway DA , et al.   The role of bladdertourethral reflexes in urinary continence mechanisms in rats . Am J Physiol Renal Physiol . 2004;287:F434–F441
  35. Strasser H , Ninkovic M , Hess M , Bartsah G , Stenzl A . Anatomic and functional studies of the male and female urethral sphincter . World J Urol . 2000;18:324–329
  36. Strasser H , Tiefenthaler M , Steinlechner M , Eder I , Bartsch G , Konwalinka G . Age dependent apoptosis and loss of rhabdosphincter cells . J Urol . 2000;164:1781–1785
  37. Pittenger MF , Mackay AM , Beck SC , et al.   Multilineage potential of adult human mesenchymal stem cells . Science . 1999;284:143–147
  38. Ferrari G , Cusella-De Angelis G , Coletta M , et al.   Muscle regeneration by bone marrowderived myogenic progenitors . Science . 1998;279:1528–1530
  39. Prockop DJ . Marrow stromal cells as stem cells for nonhematopoietic tissues . Science . 1997;276:71–74
  40. Dezawa M , Ishikawa H , Itokazu Y , et al.   Bone marrow stromal cells generate muscle cells and repair muscle degeneration . Science . 2005;309:314–317
  41. Qu Z , Balkir L , van Deutekom JC , Robbins PD . Development of approaches to improve cell survival in myoblast transfer therapy . J Cell Biol . 1998;142:1257–1267
  42. Seale P , Asakura A , Rudnicki MA . The potential of muscle stem cells . Dev Cell . 2001;1:333–342
  43. Jankowski RJ , Deasy BM , Huard J . Muscle-derived stem cells . Gene Ther . 2002;9:642–647
  44. Oshima H , Payne TR , Urish KL , et al.   Differential myocardial infarct repair with muscle stem cells compared to myoblasts . Mol Ther . 2005;12:1130–1141
  45. Lee JY , Qu-Petersen Z , Cao B , et al.   Clonal isolation of musclederived cells capable of enhancing muscle regeneration and bone healing . J Cell Biol . 2000;150:1085–1100
  46. Qu-Petersen Z , Deasy B , Jankowski R , et al.   Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration . J Cell Biol . 2002;157:851–864
  47. Yokoyama T , Yoshimura N , Dhir R , et al.   Persistence and survival of autologous muscle derived cells versus bovine collagen as potential treatment of stress urinary incontinence . J Urol . 2001;165:271–276
  48. Lee JY , Paik SY , Yuk SH , Lee JH , Ghil SH , Lee SS . Long term effects of musclederived stem cells on leak point pressure and closing pressure in rats with transected pudendal nerves . Mol Cells . 2004;18:309–313
  49. Kwon D , Kim Y , Pruchnic R , et al.   Periurethral cellular injection: comparison of musclederived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence . Urology . 2006;68:449–454
  50. Chancellor MB , Yokoyama T , Tirney S , et al.   Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility . Neurourol Urodyn . 2000;19:279–287
  51. Yokoyama T , Pruchnic R , Lee JY , et al.   Autologous primary musclederived cells transfer into the lower urinary tract . Tissue Eng . 2001;7:395–404
  52. Huard J , Yokoyama T , Pruchnic R , et al.   Muscle-derived cellmediated ex vivo gene therapy for urological dysfunction . Gene Ther . 2002;9:1617–1626
  53. Cannon TW , Lee JY , Somogyi G , et al.   Improved sphincter contractility after allogenic musclederived progenitor cell injection into the denervated rat urethra . Urology . 2003;62:958–963
  54. Chermansky CJ , Tarin T , Kwon DD , et al.   Intraurethral musclederived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency . Urology . 2004;63:780–785
  55. Beckingham IJ , Wemyss-Holden G , Lawrence WT . Long-term followup of women treated with perurethral Teflon injections for stress incontinence . Br J Urol . 1992;69:580–583
  56. Zuk PA , Zhu M , Mizuno H , et al.   Multilineage cells from human adipose tissue: implications for cellbased therapies . Tissue Eng . 2001;7:211–228
  57. Rodriguez LV , Alfonso Z , Zhang R , Leung J , Wu B , Ignarro LJ . Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells . Proc Natl Acad Sci USA . 2006;103:12167–12172
  58. Jack GS , Almeida FG , Zhang R , Alfonso ZC , Zuk PA , Rodriguez LV . Processed lipoaspirate cells for tissue engineering of the lower urinary tract: implications for the treatment of stress urinary incontinence and bladder reconstruction . J Urol . 2005;174:2041–2045
  59. Zeng X , Jack GS , Zhang R , et al.   Treatment of SUI using adipose derived stem cells: restoration of urethral function . J Urol . 2006;175:291
  60. Robbins SG , Rajaratnam VS , Penn JS . Evidence for upregulation and redistribution of vascular endothelial growth factor (VEGF) receptors flt-1 and flk-1 in the oxygeninjured rat retina . Growth Factors . 1998;16:1–9
  61. Florini JR , Ewton DZ , Magri KA . Hormones, growth factors, and myogenic differentiation . Annu Rev Physiol . 1991;53:201–216
  62. Ruberti F , Capsoni S , Comparini A , et al.   Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy . J Neurosci . 2000;20:2589–2601
  63. Rende M , Brizi E , Conner J , et al.   Nerve growth factor (NGF) influences differentiation and proliferation of myogenic cells in vitro via TrKA . Int J Dev Neurosci . 2000;18:869–885
  64. Reddypalli S , Roll K , Lee HK , Lundell M , Barea-Rodriguez E , Wheeler EF . p75NTR-mediated signaling promotes the survival of myoblasts and influences muscle strength . J Cell Physiol . 2005;204:819–829
  65. Wheeler EF , Gong H , Grimes R , Benoit D , Vazguez L . p75NTR and Trk receptors are expressed in reciprocal patterns in a wide variety of nonneural tissues during rat embryonic development, indicating independent receptor functions . J Comp Neurol . 1998;391:407–428
  66. Dedkov EI , Kostrominova TY , Borisov AB , Carlson BM . Survival of Schwann cells in chronically denervated skeletal muscles . Acta Neuropathol . 2002;103:565–574
  67. Shooter EM . Early days of the nerve growth factor proteins . Annu Rev Neurosci . 2001;24:601–629
  68. Shi H , Song CK , Giordano A , Cinti S , Bartness TJ . Sensory or sympathetic white adipose tissue denervation differentially affects depot growth and cellularity . Am J Physiol Regul Integr Comp Physiol . 2005;288:R1028–R1037
  69. Peeraully MR , Jenkins JR , Trayhurn P . NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines . Am J Physiol Endocrinol Metab . 2004;287:E331–E339
  70. Strasser H , Marksteiner R , Margreiter E , et al.   Transurethral ultrasonographyguided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence . World J Urol . 2007;25:385–392
  71. Strasser H , Pinggera GM , Gozzi C , et al.   Three-dimensional transrectal ultrasound of the male urethral rhabdosphincter . World J Urol . 2004;22:335–338
  72. Strasser H , Marksteiner R , Margreiter E , 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
  73. Mitterberger M , Pinggera GM , Marksteiner R , et al.   Adult stem cell therapy of female stress urinary incontinence . Eur Urol . 2007;53:169–175
  74. Carr LK , Steele D , Steele S , et al.   1-year follow up of autologous musclederived stem cell injection pilot study to treat stress urinary incontinence . Int Urogynecol J Pelvic Floor Dysfunct . 2008;19:881–883
  75. Ulmsten U , Johnson P , Rezapour M . A threeyear follow up of tension free vaginal tape for surgical treatment of female stress urinary incontinence . Br J Obstet Gynaecol . 1999;106:345–350
  76. Nilsson CG , Kuuva N , Falconer C , Rezapour M , Ulmsten U . Long-term results of the tensionfree vaginal tape (TVT) procedure for surgical treatment of female stress urinary incontinence . Int Urogynecol J Pelvic Floor Dysfunct . 2001;12(Suppl 2):S5–S8
  77. Jeffry L , Deval B , Birsan A , Soriano D , Darai E . Objective and subjective cure rates after tensionfree vaginal tape for treatment of urinary incontinence . Urology . 2001;58:702–706
  78. Ward KL , Hilton P . A prospective multicenter randomized trial of tensionfree vaginal tape and colposuspension for primary urodynamic stress incontinence: twoyear follow-up . Am J Obstet Gynecol . 2004;190:324–331

PII: S1016-3190(08)60032-4

doi:10.1016/S1016-3190(08)60032-4

Tzu Chi Medical Journal
Volume 20, Issue 3 , Pages 169-176, September 2008

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