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Zellbasierte Therapie der Belastungsinkontinenz

Welche Zelle zu welchen Kosten?

Cell-based therapy to treat stress urinary incontinence

Which cell type at what cost?

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Zusammenfassung

In Deutschland leiden 6–8 Mio. Frauen und Männer an Harninkontinenz, das sind 12,5 % der Bevölkerung. Bis zur Mitte des Jahrhunderts wird der Anteil der Betroffenen laut Schätzungen auf fast 30 % steigen. Der Hauptgrund dieser Entwicklung ist die Alterung der Gesellschaft, aber auch die bessere Aufklärung der Patienten und der Wunsch nach einer Therapie sind von Bedeutung. Zu den von der Krankenkasse übernommenen Kosten kommen jährlich Ausgaben von über einer halben Milliarde Euro, für welche die Patienten selbst aufkommen müssen. Zu beachten ist auch die soziale Stigmatisierung bei Inkontinenz. Die aktuell üblichen Therapieoptionen zielen auf eine Linderung der Symptome, ermöglichen aber keine funktionelle Wiederherstellung. Eine Möglichkeit könnte das „Tissue Engineering“ oder die Stammzelltherapie darstellen. Der vorliegende Beitrag erörtert die Chancen, dass dieser Behandlungsansatz die Therapie der Belastungsinkontinenz verändern wird. Grenzen und rechtliche Aspekte werden ebenso behandelt wie die voraussichtlichen Kosten. Die Behandlungskosten sind im Vergleich zu den Standardtherapieoptionen gegenwärtig zwar höher – wird hier aber gespart, trägt die Kosten indirekt die Gesellschaft.

Abstract

In Germany, 6–8 million woman and men suffer urinary incontinence, which represents 12.5 % of the population. It is estimated that by the middle of this century, it will increase to almost 30 %. The primary reason will be primarily related to the aging population but also to patient awareness and seeking a solution. In addition to the cost which is covered by the health insurance, the patient will spend more than half a billion euro/year out-of-pocket, not to mention the social stigma associated with urinary incontinence. The current common treatment options are symptomatic but do not restore functionality. One option might be tissue engineering or stem cell therapy.  This article describes the likelihood that this therapy will change the approach in treating stress urinary incontinence. Boundaries and legal aspects are highlighted as well as approximated cost. These treatment costs might be currently higher than the standard treatment options, but the investment to reduce these costs are paid indirectly by society.

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Literatur

  1. Abdel-Fattah M, Ford JA, Lim CP, Madhuvrata P (2011) Single-incision mini-slings versus standard midurethral slings in surgical management of female stress urinary incontinence: a meta-analysis of effectiveness and complications. Eur Urol 60(3):468–480

    Article  PubMed  Google Scholar 

  2. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822

    Article  CAS  PubMed  Google Scholar 

  3. Amend B, Reisenauer C, Stenzl, A, Sievert KD (2009) Treatment of female and male stress urinary incontinence. Current aspects. Urologe A 48(9):1059–1062

    Article  CAS  PubMed  Google Scholar 

  4. Battula VL, Treml S, Bareiss PM et al (2009) Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271 and mesenchymal stem cell antigen-1 (MSCA-1). Hematologica 94:19–30

    Article  Google Scholar 

  5. Cannon TW, Lee JY, Somogyi G et al (2003) Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra. Urology 62(5):958–963

    Article  PubMed  Google Scholar 

  6. Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650

    Article  CAS  PubMed  Google Scholar 

  7. Carr LK, Steele D, Steele S et al (2008) 1-year follow-up of autologous muscle-derived stem cell injection pilot study to treat stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 19(6):881–883

    Article  CAS  PubMed  Google Scholar 

  8. Cerruto MA, D’Elia C, Artibani W (2013) Continence and complications rates after male slings as primary surgery for post-prostatectomy incontinence: a systematic review. Arch Ital Urol Androl 85(2):92–95

    PubMed  Google Scholar 

  9. Chancellor MB, Yokoyama T, Tirney S et al (2000) 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 19(3):279–287

    Article  CAS  PubMed  Google Scholar 

  10. Chapman MR, Balakrishnan KR, Li J et al (2013) Sorting single satellite cells from individual myofibers reveals heterogeneity in cell-surface markers and myogenic capacity. Integr Biol (Camb) 5(4):692–702

    Article  Google Scholar 

  11. Chermansky CJ, Winters JC (2012) Complications of vaginal mesh surgery. Curr Opin Urol 22(4):287–291

    Article  PubMed  Google Scholar 

  12. Crisan M, Yap S, Casteilla L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313

    Article  CAS  PubMed  Google Scholar 

  13. Dellavalle A, Sampaolesi M, Tonlorenzi R et al (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9(3):255–267

    Article  CAS  PubMed  Google Scholar 

  14. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  15. Drost AC, Weng S, Feil G et al (2009) In vitro myogenic differentiation of human bone marrow-derived mesenchymal stem cells as a potential treatment for urethral sphincter muscle repair. Ann N Y Acad Sci 1176:135–143

    Article  CAS  PubMed  Google Scholar 

  16. Eberli D, Aboushwareb T, Soker S et al (2012) Muscle precursor cells for the restoration of irreversibly damaged sphincter function. Cell Transplant 21(9):2089–2098

    Article  PubMed  Google Scholar 

  17. Elmi A, Kajbafzadeh A-M, Tourchi A et al (2011) Safety, efficacy and health related quality of life of autologous myoblast transplantation for treatment of urinary incontinence in children with bladder exstrophy-epispadias complex. J Urol 186(5):2021–2026

    Article  PubMed  Google Scholar 

  18. Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4(5):267–274

    CAS  PubMed  Google Scholar 

  19. Fu Q, Song XF, Liao GL et al (2010) Myoblasts differentiated from adipose-derived stem cells to treat stress urinary incontinence. Urology 75(3):718–723

    Article  PubMed  Google Scholar 

  20. Fukuda K (2003) Use of adult marrow mesenchymal stem cells for regeneration of cardiomyocytes. Bone marrow transplantation 32(Suppl 1):25–27

    Article  Google Scholar 

  21. Garcia-Arranz M, Gregorio SA (2012) Phase II clinical trial to study feasibility and safety of the expanded autologous MSC derived from adipose tissue for the local feminine stress urinary incontinence. http://clinicaltrails.gov

  22. Gerullis H, Eimer C, Georgas E et al (2012) Muscle-derived cells for treatment of iatrogenic sphincter damage and urinary incontinence in men. Scientific World J 2012:6

    Article  Google Scholar 

  23. Goldman HB, Sievert KD, Damaser MS (2012) Will we ever use stem cells for the treatment of SUI? ICI-RS 2011. Neurourol Urodyn 31(3):386–389

    Article  PubMed Central  PubMed  Google Scholar 

  24. Gunetti M, Tomasi S, Giammo A et al (2012) Myogenic potential of whole bone marrow mesenchymal stem cells in vitro and in vivo for usage in urinary incontinence. PLoS One 7(9):45538

    Article  Google Scholar 

  25. Hare JM, Difede D, Heldman AW (2013) Use of stem cells for ischemic cardiomyopathy – reply. JAMA 309(14):1458–1459

    Article  CAS  PubMed  Google Scholar 

  26. Hare JM, Fishman JE, Gerstenblith G et al (2012) Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308(22):2369–2379

    Article  CAS  PubMed  Google Scholar 

  27. Hughey CC, Johnsen VL, Ma L et al (2012) Mesenchymal stem cell transplantation for the infarcted heart: a role in minimizing abnormalities in cardiac-specific energy metabolism. Am J Physiol Endocrinol Metab 302(2):163–172

    Article  Google Scholar 

  28. Jiang HH, Damaser MS (2011) Animal models of stress urinary incontinence. Handb Exp Pharmacol 202:45–67

    Article  CAS  PubMed  Google Scholar 

  29. Johnson K, Zhu S, Tremblay MS et al (2012) A stem cell-based approach to cartilage repair. Science 336(6082):717–721

    Article  CAS  PubMed  Google Scholar 

  30. Kajbafzadeh AM, Elmi A, Payabvash S et al (2008) Transurethral autologous myoblast injection for treatment of urinary incontinence in children with classic bladder exstrophy. J Urol 180(3):1098–1105

    Article  PubMed  Google Scholar 

  31. Kanematsu A, Yamamoto S, Iwai-Kanai E et al (2005) Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells. Am J Pathol 166(2):565–573

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Kerr LA (2005) Bulking agents in the treatment of stress urinary incontinence: history, outcomes, patient populations, and reimbursement profile. Rev Urol 7(Suppl 1):3–11

    Google Scholar 

  33. Kim JH, Lee SR, Song YS, Lee HJ (2013) Stem cell therapy in bladder dysfunction: where are we? And where do we have to go? Biomed Res Int 2013:930713

    PubMed Central  PubMed  Google Scholar 

  34. Kleinert S, Horton R (2008) Retraction – autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial. Lancet 372(9641):789–790

    Article  PubMed  Google Scholar 

  35. Kowalik CG, Delong JM, Mourtzinos AP (2013) The adVance transobturator male sling for post-prostatectomy incontinence: subjective and objective outcomes with 3 years follow up. Neurourol Urodyn (Epub ahead of print)

  36. Kwon D, Kim Y, Pruchnic R et al (2006) Periurethral cellular injection: comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence. Urology 68(2):449–454

    Article  PubMed  Google Scholar 

  37. Kwon D, Minnery B, Kim Y et al (2005) Neurologic recovery and improved detrusor contractility using muscle-derived cells in rat model of unilateral pelvic nerve transection. Urology 65(6):1249–1253

    Article  PubMed  Google Scholar 

  38. Lin G, Wang G, Banie L et al (2010) Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy 12(1):88–95

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Lin YC, Ko TL, Shih YH et al (2011) Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke 42(7):2045–2053

    Article  PubMed  Google Scholar 

  40. Mitterberger M, Marksteiner R, Margreiter E et al (2008) Myoblast and fibroblast therapy for post-prostatectomy urinary incontinence: 1-year followup of 63 patients. J Urol 179(1):226–231

    Article  PubMed  Google Scholar 

  41. Montarras D, Morgan J, Collins C et al (2005) Direct isolation of satellite cells for skeletal muscle regeneration. Science 309(5743):2064–2067

    Article  CAS  PubMed  Google Scholar 

  42. Pasquini MC, Wang Z, Horowitz MM, Gale RP (2010) 2010 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders. Clin Transpl 28:87–105

    Google Scholar 

  43. Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair – current views. Stem Cells 25(11):2896–2902

    Article  PubMed  Google Scholar 

  44. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  CAS  PubMed  Google Scholar 

  45. Rackwitz L, Eden L, Reppenhagen S et al (2012) Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head. Stem Cell Res Ther 3(1):7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Sathianathen N, Moon D, McGuigan S (2013) Outcomes of Artificial Urinary Sphincter Implantation in the Irradiated Patient. BJU Int (Epub ahead of print)

  47. Scott FB, Bradley WE, Timm GW (1973) Treatment of urinary incontinence by implantable prosthetic sphincter. Urology 1(3):252–259

    Article  CAS  PubMed  Google Scholar 

  48. Sievert KD, Amend B, Stenzl A (2007) Tissue engineering for the lower urinary tract: a review of a state of the art approach. Eur Urol 52(6):1580–1589

    Article  PubMed  Google Scholar 

  49. Staack A, Rodriguez LV (2011) Stem cells for the treatment of urinary incontinence. Curr Urol Rep 12(1):41–46

    Article  PubMed Central  PubMed  Google Scholar 

  50. Strasser H, Marksteiner R, Margreiter E et al (2007) Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial. Lancet 369(9580):2179–2186

    Article  CAS  PubMed  Google Scholar 

  51. Strasser H, Tiefenthaler M, Steinlechner M et al (1999) Urinary incontinence in the elderly and age-dependent apoptosis of rhabdosphincter cells. Lancet 354(9182):918–919

    Article  CAS  PubMed  Google Scholar 

  52. Subak LL, Brubaker L, Chai TC et al (2008) High costs of urinary incontinence among women electing surgery to treat stress incontinence. Obstet Gynecol 111(4):899–907

    Article  PubMed Central  PubMed  Google Scholar 

  53. Teixeira FG, Carvalho MM, Sousa N, Salgado AJ (2013) Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci 23;10(1):106

    Google Scholar 

  54. Tolar J, Le Blanc K, Keating A, Blazar BR (2010) Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells 28(8):1446–1455

    Article  PubMed Central  PubMed  Google Scholar 

  55. Trost L, Elliott DS (2012) Male stress urinary incontinence: a review of surgical treatment options and outcomes. Adv Urol 2012:287489

    Article  PubMed Central  PubMed  Google Scholar 

  56. Ulrich C, Rolauffs B, Abele H et al (2013) Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors Runx2 and Twist2. Stem Cells Dev (in press)

  57. Vaegler M, Lenis AT, Daum L et al (2012) Stem cell therapy for voiding and erectile dysfunction. Nature reviews. Urology 22:2859–2872

    Google Scholar 

  58. Vakalopoulos I, Kampantais S, Laskaridis L et al (2012) New artificial urinary sphincter devices in the treatment of male iatrogenic incontinence. Adv Urol 2012:439372

    Article  PubMed Central  PubMed  Google Scholar 

  59. Wagers AJ, Conboy IM (2005) Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell 122(5):659–667

    Article  CAS  PubMed  Google Scholar 

  60. Wallner C, Dabhoiwala NF, DeRuiter MC, Lamers WH (2009) The anatomical components of urinary continence. Eur Urol 55(4):932–943

    Article  PubMed  Google Scholar 

  61. Yamamoto T, Gotoh M, Hattori R et al (2010) Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases. Int J Urol 17(1):75–82

    Article  PubMed  Google Scholar 

  62. Yiou R, Lefaucheur JP, Atala A (2003) The regeneration process of the striated urethral sphincter involves activation of intrinsic satellite cells. Anat Embryol (Berl) 206(6):429–435

    Google Scholar 

  63. Zhang GY, Li QF, Fu XB (2013) Use of stem cells for ischemic cardiomyopathy. JAMA 309(14):1458

    Article  CAS  PubMed  Google Scholar 

  64. Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228

    Article  CAS  PubMed  Google Scholar 

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Danksagung

Die Autoren danken dem BMBF und der DFG für die Unterstützung ihrer Forschungsprojekte, soweit sie am Rande in diese Übersichtsarbeit eingegangen sind.

Einhaltung ethischer Richtlinien

Interessenkonflikt. Martin Vaegler, Luis Arenas DaSilva, Karin Benz, Bastian Amend, Jürgen Mollenhauer, Wilhelm K. Aicher, Arnulf Stenzl und Karl-Dietrich Sievert geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinische Forschergruppe 273, Universitätsklinik für Urologie, Tübingen, Deutschland

    M. Vaegler, L.A. DaSilva & W.K. Aicher

  2. Universitätsklinik für Urologie, Eberhard-Karls-Universität Tübingen, Hoppe-Seyler-Straße 15, 72076, Tübingen, Deutschland

    B. Amend, A. Stenzl &  K.-D. Sievert

  3. Naturwissenschaftliches und Medizinisches Institut, Universität Tübingen, Reutlingen, Deutschland

    K. Benz & J. Mollenhauer

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  1. M. Vaegler
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  2. L.A. DaSilva
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  3. K. Benz
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  4. B. Amend
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  5. J. Mollenhauer
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  7. A. Stenzl
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  8. K.-D. Sievert
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Vaegler, M., DaSilva, L., Benz, K. et al. Zellbasierte Therapie der Belastungsinkontinenz. Urologe 53, 354–361 (2014). https://doi.org/10.1007/s00120-013-3353-8

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