Skip to main content

Advertisement

SpringerLink
Log in

Tissue-Engineered Urinary Conduits

  • Regenerative Medicine (A Atala, Section Editor)
  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

The role of tissue engineering in the cystectomy population rests on the principle of sparing healthy intestinal tissue while replacing diseased bladder. Over the last 25 years advances in cell biology and material science have improved the quality and durability of bladder replacement in animals. The neo-urinary conduit ([NUC]-Tengion) employs autologous fat smooth muscle cells which are seeded onto synthetic, biodegradable scaffolds. This seeded construct is then implanted in the patient and purportedly regenerates native urinary tissue to serve as a passive channel connecting the ureters to the skin surface. Preclinical animal studies as well as the first phase I human trial implanting the NUC are reviewed. While the ultimate goal of creating a durable, effective, tissue-engineered conduit is still in its infancy, important technical and experimental strides have been made.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent). 2009;22:377–84.

    Google Scholar 

  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  3. Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009;27:289–93.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Based on unpublished analyses in the American College of Surgeons National Surgical Quality Improvement Program Dataset. Shabsigh A, Korets R, Vora KC et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009;55: 164-174.

  5. Farnham SB, Cookson MS, Alberts G, Smith Jr JA, Chang SS. Benefit of radical cystectomy in the elderly patient with significant co-morbidities. Urol Oncol. 2004;22:178–81.

    Article  PubMed  Google Scholar 

  6. Kim SP, Shah ND, Weight CJ, et al. Population-based trends in urinary diversion among patients undergoing radical cystectomy for bladder cancer. BJU Int. 2013;112:478–84.

    Article  PubMed  Google Scholar 

  7. Kim BS, Baez CE, Atala A. Biomaterials for tissue engineering. World J Urol. 2000;18:2–9.

    Article  CAS  PubMed  Google Scholar 

  8. Farhat WA, Yeger H. Does mechanical stimulation have any role in urinary bladder tissue engineering? World J Urol. 2008;26:301–5.

    Article  PubMed  Google Scholar 

  9. Kim BS, Mooney DJ. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 1998;16:224–30.

    Article  CAS  PubMed  Google Scholar 

  10. Song L, Murphy SV, Yang B, Xu Y, Zhang Y, Atala A. Bladder acellular matrix and its application in bladder augmentation. Tissue Eng Part B, Rev. 2014;20:163–72.

    Article  CAS  Google Scholar 

  11. Sutherland RS, Baskin LS, Hayward SW, Cunha GR. Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix. J Urol. 1996;156:571–7.

    Article  CAS  PubMed  Google Scholar 

  12. Yang B, Zhang Y, Zhou L, et al. Development of a porcine bladder acellular matrix with well-preserved extracellular bioactive factors for tissue engineering. Tissue Eng Part C, Methods. 2010;16:1201–11.

    Article  CAS  Google Scholar 

  13. Chun SY, Lim GJ, Kwon TG, et al. Identification and characterization of bioactive factors in bladder submucosa matrix. Biomaterials. 2007;28:4251–6.

    Article  CAS  PubMed  Google Scholar 

  14. Chen F, Yoo JJ, Atala A. Acellular collagen matrix as a possible "off the shelf" biomaterial for urethral repair. Urology. 1999;54:407–10.

    Article  CAS  PubMed  Google Scholar 

  15. Horst M, Madduri S, Gobet R, et al. Engineering functional bladder tissues. J Tissue Eng Regen Med. 2013;7:515–22.

    Article  CAS  PubMed  Google Scholar 

  16. Engelhardt EM, Stegberg E, Brown RA, et al. Compressed collagen gel: a novel scaffold for human bladder cells. J Tissue Eng Regen Med. 2010;4:123–30.

    Article  CAS  PubMed  Google Scholar 

  17. Mauney JR, Cannon GM, Lovett ML, et al. Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation. Biomaterials. 2011;32:808–18.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Ajalloueian F, Zeiai S, Fossum M, Hilborn JG. Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion. Biomaterials. 2014;35:5741–8.

    Article  CAS  PubMed  Google Scholar 

  19. Pattison MA, Wurster S, Webster TJ, Haberstroh KM. Three-dimensional, nano-structured PLGA scaffolds for bladder tissue replacement applications. Biomaterials. 2005;26:2491–500.

    Article  CAS  PubMed  Google Scholar 

  20. Webb AR, Yang J, Ameer GA. Biodegradable polyester elastomers in tissue engineering. Exp Opin Biol Ther. 2004;4:801–12.

    Article  CAS  Google Scholar 

  21. Heffernan MJ, Murthy N. Polyketal nanoparticles: a new pH-sensitive biodegradable drug delivery vehicle. Bioconjugate Chem. 2005;16:1340–2.

    Article  CAS  Google Scholar 

  22. Engelhardt EM, Micol LA, Houis S, et al. A collagen-poly(lactic acid-co-varepsilon-caprolactone) hybrid scaffold for bladder tissue regeneration. Biomaterials. 2011;32:3969–76.

    Article  CAS  PubMed  Google Scholar 

  23. Eberli D, Freitas Filho L, Atala A, Yoo JJ. Composite scaffolds for the engineering of hollow organs and tissues. Methods. 2009;47:109–15.

    Article  CAS  PubMed  Google Scholar 

  24. Basu J, Jayo MJ, Ilagan RM, et al. Regeneration of native-like neo-urinary tissue from nonbladder cell sources. Tissue Eng Part A. 2012;18:1025–34.

    Article  CAS  PubMed  Google Scholar 

  25. Drewa T. The artificial conduit for urinary diversion in rats: a preliminary study. Transplant Proc. 2007;39:1647–51.

    Article  CAS  PubMed  Google Scholar 

  26. Geutjes P, Roelofs L, Hoogenkamp H, et al. Tissue engineered tubular construct for urinary diversion in a preclinical porcine model. J Urol. 2012;188:653–60. This study represents one of the first preclinical animal models of a collagen-polymer conduit being utilized for bladder replacement.

    Article  CAS  PubMed  Google Scholar 

  27. Liao W, Yang S, Song C, et al. Tissue-engineered tubular graft for urinary diversion after radical cystectomy in rabbits. J Surg Res. 2013;182:185–91.

    Article  PubMed  Google Scholar 

  28. Sloff M, de Vries R, Geutjes P, et al. Tissue engineering in animal models for urinary diversion: a systematic review. PLoS One. 2014;9:e98734.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Bodin A, Bharadwaj S, Wu S, Gatenholm P, Atala A, Zhang Y. Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion. Biomaterials. 2010;31:8889–901.

    Article  CAS  PubMed  Google Scholar 

  30. Reinfeldt Engberg G, Lundberg J, Chamorro CI, Nordenskjold A, Fossum M. Transplantation of autologous minced bladder mucosa for a one-step reconstruction of a tissue engineered bladder conduit. Biomed Res Int. 2013;2013:212734.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Oberpenning F, Meng J, Yoo JJ, Atala A. De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nat Biotechnol. 1999;17:149–55.

    Article  CAS  PubMed  Google Scholar 

  32. Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet. 2006;367:1241–6.

    Article  PubMed  Google Scholar 

  33. Liao WB, Song C, Li YW, Yang SX, Meng LC, Li XH. Tissue-engineered conduit using bladder acellular matrix and bladder epithelial cells for urinary diversion in rabbits. Chin Med J (Engl). 2013;126:335–9.

    Google Scholar 

  34. Baumert H, Simon P, Hekmati M, et al. Development of a seeded scaffold in the great omentum: feasibility of an in vivo bioreactor for bladder tissue engineering. Eur Urol. 2007;52:884–90.

    Article  PubMed  Google Scholar 

  35. Drewa T, Adamowicz J, Sharma A. Tissue engineering for the oncologic urinary bladder. Nat Rev Urol. 2012;9:561–72.

    Article  CAS  PubMed  Google Scholar 

  36. Aboushwareb T, Atala A. Stem cells in urology. Nat Clin Pract Urol. 2008;5:621–31.

    Article  CAS  PubMed  Google Scholar 

  37. Drewa T, Adamowicz J, Sharma A. Tissue engineering for the oncologic urinary bladder. Nat Rev Urol. 2012;9:561–72.

    Article  CAS  PubMed  Google Scholar 

  38. Frimberger D, Morales N, Gearhart JD, Gearhart JP, Lakshmanan Y. Human embryoid body-derived stem cells in tissue engineering-enhanced migration in co-culture with bladder smooth muscle and urothelium. Urology. 2006;67:1298–303.

    Article  PubMed  Google Scholar 

  39. Frimberger D, Morales N, Shamblott M, Gearhart JD, Gearhart JP, Lakshmanan Y. Human embryoid body-derived stem cells in bladder regeneration using rodent model. Urology. 2005;65:827–32.

    Article  PubMed  Google Scholar 

  40. Lakshmanan Y, Frimberger D, Gearhart JD, Gearhart JP. Human embryoid body-derived stem cells in co-culture with bladder smooth muscle and urothelium. Urology. 2005;65:821–6.

    Article  PubMed  Google Scholar 

  41. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  42. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  CAS  PubMed  Google Scholar 

  43. Moad M, Pal D, Hepburn AC, et al. A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells. Eur Urol. 2013;64:753–61.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Osborn SL, Thangappan R, Luria A, Lee JH, Nolta J, Kurzrock EA. Induction of human embryonic and induced pluripotent stem cells into urothelium. Stem Cells Transl Med. 2014;3:610–9.

    Article  CAS  PubMed  Google Scholar 

  45. Adamowicz J, Kowalczyk T, Drewa T. Tissue engineering of urinary bladder—current state of art and future perspectives. Cent Eur J Urol. 2013;66:202–6.

    Google Scholar 

  46. Sharma AK. An examination of regenerative medicine-based strategies for the urinary bladder. Regen Med. 2011;6:583–98.

    Article  PubMed  Google Scholar 

  47. 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;174:353–9.

    Article  PubMed  Google Scholar 

  48. Zhang Y, Lin HK, Frimberger D, Epstein RB, Kropp BP. Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder. BJU Int. 2005;96:1120–5.

    Article  CAS  PubMed  Google Scholar 

  49. Matsunuma H, Kagami H, Narita Y, et al. Constructing a tissue-engineered ureter using a decellularized matrix with cultured uroepithelial cells and bone marrow-derived mononuclear cells. Tissue Eng. 2006;12:509–18.

    Article  CAS  PubMed  Google Scholar 

  50. Imamura T, Yamamoto T, Ishizuka O, Gotoh M, Nishizawa O. The microenvironment of freeze-injured mouse urinary bladders enables successful tissue engineering. Tissue Eng Part A. 2009;15:3367–75.

    Article  CAS  PubMed  Google Scholar 

  51. Sharma AK, Hota PV, Matoka DJ, et al. Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films. Biomaterials. 2010;31:6207–17.

    Article  CAS  PubMed  Google Scholar 

  52. Sharma AK, Bury MI, Marks AJ, et al. A nonhuman primate model for urinary bladder regeneration using autologous sources of bone marrow-derived mesenchymal stem cells. Stem Cells. 2011;29:241–50.

    Article  CAS  PubMed  Google Scholar 

  53. Burt RK. Clinical utility in maximizing CD34+ cell count in stem cell grafts. Stem Cells. 1999;17:373–6.

    Article  CAS  PubMed  Google Scholar 

  54. Jack GS, Zhang R, Lee M, Xu Y, Wu BM, Rodríguez LV. Urinary bladder smooth muscle engineered from adipose stem cells and a three dimensional synthetic composite. Biomaterials. 2009;30:3259–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Shi JG, Fu WJ, Wang XX et al. Transdifferentiation of human adipose-derived stem cells into urothelial cells: potential for urinary tract tissue engineering. Cell Tissue Res. 2012.

  56. Zhang M, Peng Y, Zhou Z, Zhou J, Wang Z, Lu M. Differentiation of human adipose-derived stem cells co-cultured with urothelium cell line toward a urothelium-like phenotype in a nude murine model. Urology. 2013;81:465. e15-465. e22.

    PubMed  Google Scholar 

  57. Drewa T, Joachimiak R, Kaznica A, Sarafian V, Pokrywczynska M. Hair stem cells for bladder regeneration in rats: preliminary results. Transplant Proc. 2009;41:4345–51.

    Article  CAS  PubMed  Google Scholar 

  58. Drewa T, Joachimiak R, Bajek A, et al. Hair follicle stem cells can be driven into a urothelial-like phenotype: an experimental study. Int J Urol. 2013;20:537–42.

    Article  CAS  PubMed  Google Scholar 

  59. Shoae-Hassani A, Sharif S, Seifalian AM, Mortazavi-Tabatabaei SA, Rezaie S, Verdi J. Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women. BJU Int. 2013;112:854–63.

    Article  CAS  PubMed  Google Scholar 

  60. Kang HH, Kang JJ, Kang HG, Chung SS. Urothelial differentiation of human amniotic fluid stem cells by urothelium specific conditioned medium. Cell Biol Int. 2014;38:531–7.

    Article  CAS  PubMed  Google Scholar 

  61. De Coppi P, Callegari A, Chiavegato A, et al. Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cryo-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells. J Urol. 2007;177:369–76.

    Article  PubMed  Google Scholar 

  62. Hyndman ME, Kaye D, Field NC, et al. The use of regenerative medicine in the management of invasive bladder cancer. Adv Urol. 2012;2012:653652.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res. 2001;49:568–81.

    Article  CAS  PubMed  Google Scholar 

  64. Loai Y, Yeger H, Coz C, et al. Bladder tissue engineering: tissue regeneration and neovascularization of HAVEGF-incorporated bladder acellular constructs in mouse and porcine animal models. J Biomed Mater Res, Part A. 2010;94:1205–15.

    Google Scholar 

  65. Lorentz KM, Yang L, Frey P, Hubbell JA. Engineered insulin-like growth factor-1 for improved smooth muscle regeneration. Biomaterials. 2012;33:494–503.

    Article  CAS  PubMed  Google Scholar 

  66. Bharadwaj S, Liu G, Shi Y, et al. Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue Eng Part A. 2011;17:2123–32.

    Article  PubMed  Google Scholar 

  67. Wu R, Liu G, Bharadwaj S, Zhang Y. Isolation and myogenic differentiation of mesenchymal stem cells for urologic tissue engineering. In: Organ regeneration. Springer; 2013: 65-80

  68. Sangha N. Isolation of urothelial cells from bladder tissue. In: Organ regeneration. Springer; 2013: 21-33

  69. Novosel EC, Kleinhans C, Kluger PJ. Vascularization is the key challenge in tissue engineering. Adv Drug Deliv Rev. 2011;63:300–11.

    Article  CAS  PubMed  Google Scholar 

  70. Liebermann-Meffert D. The greater omentum. Anatomy, embryology, and surgical applications. Surg Clin North Am. 2000;80:275–93.

    Article  CAS  PubMed  Google Scholar 

  71. Schultheiss D, Gabouev AI, Cebotari S, et al. Biological vascularized matrix for bladder tissue engineering: matrix preparation, reseeding technique and short-term implantation in a porcine model. J Urol. 2005;173:276–80.

    Article  PubMed  Google Scholar 

  72. Cartwright L, Farhat WA, Sherman C, et al. Dynamic contrast-enhanced MRI to quantify VEGF-enhanced tissue-engineered bladder graft neovascularization: pilot study. J Biomed Mater Res A. 2006;77:390–5.

    Article  PubMed  Google Scholar 

  73. Nomi M, Miyake H, Sugita Y, Fujisawa M, Soker S. Role of growth factors and endothelial cells in therapeutic angiogenesis and tissue engineering. Curr Stem Cell Res Ther. 2006;1:333–43.

    Article  CAS  PubMed  Google Scholar 

  74. Mondalek FG, Ashley RA, Roth CC, et al. Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: from fabrication to preclinical validation. J Biomed Mater Res A. 2010;94:712–9.

    PubMed  Google Scholar 

  75. Feil G, Christ-Adler M, Maurer S, et al. Investigations of urothelial cells seeded on commercially available small intestine submucosa. Eur Urol. 2006;50:1330–7.

    Article  PubMed  Google Scholar 

  76. Bivalacqua T, Steinberg G, Smith N, et al. mp61-16 pre-clinical and clinical translation of a tissue engineered neo-urinary conduit using adipose derived smooth muscle cells for urinary reconstruction. J Urol. 2014;191:e689.

    Article  Google Scholar 

  77. Bivalacqua T, Steinberg G, Smith N et al. 178 pre-clinical and clinical translation of a tissue engineered neo-urinary conduit using adipose derived smooth muscle cells for urinary reconstruction. European Urology Supplements. 2014;13.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Max Kates, Dr. Anirudha Singh, Dr. Hotaka Matsui, Dr. Gary D. Steinberg, Dr. Norm D. Smith, Dr. Mark P. Schoenberg, and Dr. Trinity J. Bivalacqua each declare no potential conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, 1800 Orleans Street, Marburg 134, Baltimore, MD, 21287, USA

    Max Kates, Anirudha Singh, Hotaka Matsui & Trinity J Bivalacqua

  2. Urology, University of Chicago, Chicago, IL, USA

    Gary D. Steinberg & Norm D. Smith

  3. Urology, Albert Einstein College of Medicine, New York, NY, USA

    Mark P. Schoenberg

Authors
  1. Max Kates
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anirudha Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hotaka Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gary D. Steinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norm D. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark P. Schoenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Trinity J Bivalacqua
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Max Kates.

Additional information

This article is part of the Topical Collection on Regenerative Medicine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kates, M., Singh, A., Matsui, H. et al. Tissue-Engineered Urinary Conduits. Curr Urol Rep 16, 8 (2015). https://doi.org/10.1007/s11934-015-0480-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11934-015-0480-3

Keywords

Search

Navigation