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Regenerative medicine and the neurogenic bladder

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Abstract

Control of normal bladder function by the nervous system has been described in great detail. In some cases of injury to the spinal cord, neurogenic bladder dysfunction develops, typified by detrusor sphincter dyssynergia and decreasing bladder capacity and compliance. Numerous therapies, including anticholinergic agents, botulinum toxin, neuromodulation, and clean intermittent catheterization, have been used to maintain physiologic pressures in the neurogenic bladder. When bladder compliance falls to a dangerous level despite these treatments, enterocystoplasty has been the gold-standard therapy. Although this procedure increases bladder capacity and compliance, it has been plagued by complications, such as metabolic disorders, perforations, excessive mucous productions, and stones. Recently, the field of regenerative medicine has offered novel and improved therapies for this chronic condition. This review summarizes these recent advances.

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References and Recommended Reading

  1. Wein AJ: Classification of neurogenic voiding dysfunction. J Urol 1981, 125:605–609.

    PubMed  CAS  Google Scholar 

  2. Gough DC: Enterocystoplasty. BJU Int 2001, 88:739–743.

    Article  PubMed  CAS  Google Scholar 

  3. Atala A: Tissue engineering for the replacement of organ function in the genitourinary system. Am J Transplant 2004, 4:58–73.

    Article  PubMed  CAS  Google Scholar 

  4. McGuire EJ, Woodside JR, Borden TA, et al.: Prognostic value of urodynamic testing in myelodysplastic patients. 1981. J Urol 2002, 167:1049–1053; discussion 1054.

    Article  PubMed  Google Scholar 

  5. Staack A, Hayward SW, Baskin LS, et al.: Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration. Differentiation 2005, 73:121–133.

    Article  PubMed  CAS  Google Scholar 

  6. Gilbert SM, Hensle TW: Metabolic consequences and long-term complications of enterocystoplasty in children: a review. J Urol 2005, 173:1080–1086.

    Article  PubMed  Google Scholar 

  7. Chen F, Yoo JJ, Atala A: Acellular collagen matrix as a possible “off the shelf” biomaterial for urethral repair. Urology 1999, 54:407–410.

    Article  PubMed  CAS  Google Scholar 

  8. Dahms SE, Piechota HJ, Dahiya R, et al.: Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human. Br J Urol 1998, 82:411–419.

    PubMed  CAS  Google Scholar 

  9. Piechota HJ, Dahms SE, Nunes LS, et al.: In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft. J Urol 1998, 159:1717–1724.

    Article  PubMed  CAS  Google Scholar 

  10. Yoo JJ, Meng J, Oberpenning F, et al.: Bladder augmentation using allogenic bladder submucosa seeded with cells. Urology 1998, 51:221–225.

    Article  PubMed  CAS  Google Scholar 

  11. Amiel GE, Atala A: Current and future modalities for functional renal replacement. Urol Clin North Am 1999, 26:235–246.

    PubMed  CAS  Google Scholar 

  12. Cilento BG, Freeman MR, Schneck FX, et al.: Phenotypic and cytogenetic characterization of human bladder urothelial expanded in vitro. J Urol 1994, 152:665–670.

    PubMed  CAS  Google Scholar 

  13. Fauza DO, Fishman SJ, Mehegan K, et al.: Videofetoscopically assisted fetal tissue engineering: bladder augmentation. J Pediatr Surg 1998, 33:7–12.

    Article  PubMed  CAS  Google Scholar 

  14. Godbey WT, Atala A: In vitro systems for tissue engineering. Ann N Y Acad Sci 2002, 961:10–26.

    Article  PubMed  CAS  Google Scholar 

  15. Kershen RT, Atala A: New advances in injectable therapies for the treatment of incontinence and vesicoureteral reflux. Urol Clin North Am 1999, 26:81–94.

    Article  PubMed  CAS  Google Scholar 

  16. Park HJ, Yoo JJ, Kershen RT, et al.: Reconstitution of human corporal smooth muscle and endothelial cells in vivo. J Urol 1999, 162:1106–1109.

    Article  PubMed  CAS  Google Scholar 

  17. Liebert M, Hubbel A, Chung M, et al.: Expression of mal is associated with urothelial differentiation in vitro: identification by differential display reverse-transcriptase polymerase chain reaction. Differentiation 1997, 61:177–185.

    Article  PubMed  CAS  Google Scholar 

  18. Puthenveettil JA, Burger MS, Reznikoff CA: Replicative senescence in human uroepithelial cells. Adv Exp Med Biol 1999, 462:83–91.

    PubMed  CAS  Google Scholar 

  19. Scriven SD, Booth C, Thomas DF, et al.: Reconstitution of human urothelium from monolayer cultures. J Urol 1997, 158:1147–1152.

    Article  PubMed  CAS  Google Scholar 

  20. Freeman MR, Yoo JJ, Raab G, et al.: Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder. J Clin Invest 1997, 99:1028–1036.

    Article  PubMed  CAS  Google Scholar 

  21. Nguyen HT, Park JM, Peters CA, et al.: Cell-specific activation of the HB-EGF and ErbB1 genes by stretch in primary human bladder cells. In Vitro Cell Dev Biol Anim 1999, 35:371–375.

    Article  PubMed  CAS  Google Scholar 

  22. Harriss DR: Smooth muscle cell culture: a new approach to the study of human detrusor physiology and pathophysiology. Br J Urol 1995, 75:18–26.

    PubMed  Google Scholar 

  23. Lobban ED, Smith BA, Hall GD, et al.: Uroplakin gene expression by normal and neoplastic human urothelium. Am J Pathol 1998, 153:1957–1967.

    PubMed  CAS  Google Scholar 

  24. Rackley RR, Bandyopadhyay SK, Fazeli-Matin S, et al.: Immunoregulatory potential of urothelium: characterization of NF-kappaB signal transduction. J Urol 1999, 162:1812–1816.

    Article  PubMed  CAS  Google Scholar 

  25. Oberpenning F, Meng J, Yoo JJ, et al.: De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nat Biotechnol 1999, 17:149–155.

    Article  PubMed  CAS  Google Scholar 

  26. Kim BS, Mooney DJ: Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol 1998, 16:224–230.

    Article  PubMed  CAS  Google Scholar 

  27. Bergsma JE, Rozema FR, Bos RR, et al.: In vivo degradation and biocompatibility study of in vitro pre-degraded as-polymerized polyactide particles. Biomaterials 1995, 16:267–274.

    Article  PubMed  CAS  Google Scholar 

  28. Hynes RO: Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992, 69:11–25.

    Article  PubMed  CAS  Google Scholar 

  29. Pariente JL, Kim BS, Atala A: In vitro biocompatibility assessment of naturally derived and synthetic biomaterials using normal human urothelial cells. J Biomed Mater Res 2001, 55:33–39.

    Article  PubMed  CAS  Google Scholar 

  30. Pariente JL, Kim BS, Atala A: In vitro biocompatibility evaluation of naturally derived and synthetic biomaterials using normal human bladder smooth muscle cells. J Urol 2002, 167:1867–1871.

    Article  PubMed  Google Scholar 

  31. Atala A, Bauer SB, Soker S, et al.: Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 2006, 367:1241–1246.

    Article  PubMed  Google Scholar 

  32. Nakanishi Y, Chen G, Komuro H, et al.: Tissue-engineered urinary bladder wall using PLGA mesh-collagen hybrid scaffolds: a comparison study of collagen sponge and gel as a scaffold. J Pediatr Surg 2003, 38:1781–1784.

    Article  PubMed  Google Scholar 

  33. Folkman J, Hochberg M: Self-regulation of growth in three dimensions. J Exp Med 1973, 138:745–753.

    Article  PubMed  CAS  Google Scholar 

  34. Laschke MW, Harder Y, Amon M, et al.: Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. Tissue Eng 2006, 12:2093–2104.

    Article  PubMed  CAS  Google Scholar 

  35. McDougal WS: Electrolyte abnormalities as a consequence of urinary intestinal diversion. Scand J Urol Nephrol 1992, 142:30–33.

    CAS  Google Scholar 

  36. Blandy JP: The feasibility of preparing an ideal substitute for the urinary bladder. Ann R Coll Surg Engl 1964, 35:287–311.

    PubMed  CAS  Google Scholar 

  37. Salle JL, Fraga JC, Lucib A, et al.: Seromuscular enterocystoplasty in dogs. J Urol 1990, 144:454–456; discussion 460.

    PubMed  CAS  Google Scholar 

  38. Cheng E, Rento R, Grayhack JT, et al.: Reversed seromuscular flaps in the urinary tract in dogs. J Urol 1994, 152:2252–2257.

    PubMed  CAS  Google Scholar 

  39. Dewan PA: Autoaugmentation demucosalized enterocystoplasty. World J Urol 1998, 16:255–261.

    Article  PubMed  CAS  Google Scholar 

  40. Aktug T, Ozdemir T, Agartan C, et al.: Experimentally prefabricated bladder. J Urol 2001, 165:2055–2058.

    Article  PubMed  CAS  Google Scholar 

  41. Kropp BP, Rippy MK, Badylak SF, et al.: Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologic assessment in long-term canine bladder augmentations. J Urol 1996, 155:2098–2104.

    Article  PubMed  CAS  Google Scholar 

  42. Urakami S, Shiina H, Enokida H, et al.: Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat. World J Urol 2007, 25:207–213.

    Article  PubMed  Google Scholar 

  43. Obara T, Matsuura S, Narita S, et al.: Bladder acellular matrix grafting regenerates urinary bladder in the spinal cord injury rat. Urology 2006, 68:892–897.

    Article  PubMed  Google Scholar 

  44. Badylak SF, Lantz GC, Coffey A, et al.: Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res 1989, 47:74–80.

    Article  PubMed  CAS  Google Scholar 

  45. Kropp BP, Cheng EY, Lin HK, et al.: Reliable and reproducible bladder regeneration using unseeded distal small intestinal submucosa. J Urol 2004, 172:1710–1713.

    Article  PubMed  Google Scholar 

  46. Sutherland RS, Baskin LS, Hayward SW, et al.: Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix. J Urol 1996, 156:571–577.

    Article  PubMed  CAS  Google Scholar 

  47. Probst M, Dahiya R, Carrier S, et al.: Reproduction of functional smooth muscle tissue and partial bladder replacement. Br J Urol 1997, 79:505–515.

    PubMed  CAS  Google Scholar 

  48. Portis AJ, Elbahnasy AM, Shalhav AL, et al.: Laparoscopic augmentation cystoplasty with different biodegradable grafts in an animal model. J Urol 2000, 164:1405–1411.

    Article  PubMed  CAS  Google Scholar 

  49. Landman J, Olweny E, Sundaram CP, et al.: Laparoscopic mid sagittal hemicystectomy and bladder reconstruction with small intestinal submucosa and reimplantation of ureter into small intestinal submucosa: 1-year followup. J Urol 2004, 171:2450–2455.

    Article  PubMed  Google Scholar 

  50. Kanematsu A, Yamamoto S, Ogawa O: Changing concepts of bladder regeneration. Int J Urol 2007, 14:673–678.

    Article  PubMed  Google Scholar 

  51. Zhang Y, Kropp BP, Lin HK, et al.: Bladder regeneration with cell-seeded small intestinal submucosa. Tissue Eng 2004, 10:181–187.

    Article  PubMed  Google Scholar 

  52. Chung SY, Krivorov NP, Rausei V, et al.: Bladder reconstitution with bone marrow derived stem cells seeded on small intestinal submucosa improves morphological and molecular composition. J Urol 2005, 174:353–359.

    Article  PubMed  Google Scholar 

  53. Zhang Y, Frimberger D, Cheng EY, et al.: Challenges in a larger bladder replacement with cell-seeded and unseeded small intestinal submucosa grafts in a subtotal cystectomy model. BJU Int 2006, 98:1100–1105.

    Article  PubMed  Google Scholar 

  54. Lin HK, Cowan R, Moore P, et al.: Characterization of neuropathic bladder smooth muscle cells in culture. J Urol 2004, 171:1348–1352.

    Article  PubMed  Google Scholar 

  55. Dozmorov MG, Kropp BP, Hurst RE, et al.: Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder. J Smooth Muscle Res 2007, 43:55–72.

    Article  PubMed  Google Scholar 

  56. Lai JY, Yoon CY, Yoo JJ, et al.: Phenotypic and functional characterization of in vivo tissue engineered smooth muscle from normal and pathological bladders. J Urol 2002, 168:1853–1857; discussion 1858.

    Article  PubMed  Google Scholar 

  57. Zhang Y, Lin HK, Frimberger D, et al.: Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder. BJU Int 2005, 96:1120–1125.

    Article  PubMed  CAS  Google Scholar 

  58. Mitsui T, Fischer I, Shumsky JS, et al.: Transplants of fibroblasts expressing BDNF and NT-3 promote recovery of bladder and hindlimb function following spinal contusion injury in rats. Exp Neurol 2005, 194:410–431.

    Article  PubMed  CAS  Google Scholar 

  59. Mitsui T, Kakizaki H, Tanaka H, et al.: Immortalized neural stem cells transplanted into the injured spinal cord promote recovery of voiding function in the rat. J Urol 2003, 170:1421–1425.

    Article  PubMed  Google Scholar 

  60. Mitsui T, Shumsky JS, Lepore AC, et al.: Transplantation of neuronal and glial restricted precursors into contused spinal cord improves bladder and motor functions, decreases thermal hypersensitivity, and modifies intraspinal circuitry. J Neurosci 2005, 25:9624–9636.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Steve J. Hodges.

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Hodges, S.J., Atala, A. Regenerative medicine and the neurogenic bladder. Curr Bladder Dysfunct Rep 3, 67–74 (2008). https://doi.org/10.1007/s11884-008-0011-x

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