Skip to main content
SpringerLink
Log in

Future Prospects for Human Tissue Engineered Urethra Transplantation: Decellularization and Recellularization-Based Urethra Regeneration

  • Reproductive Tissue Engineering
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

To evaluate the histological characteristics of decellularized human urethra after transplantation into the rat omentum and compare in vivo cell seeding with perfusion-based and cell sheet urethral regeneration. Eight adult human male urethras accompanied with the surrounding corpus spongiosum were obtained. The tissues were decellularized with detergent-based method. The efficacy of decellularization and extracellular matrix preservation was evaluated by several techniques. Decellularized scaffolds were transplanted into the omentum of 12 male rats and located into the scrotum. Biopsies were taken 1, 3, and 6 months postoperatively to assess the natural recellularization. Mesenchymal stem cells obtained from preputial tissue were seeded with perfusion-based and cell sheet techniques as well. Immunohistochemical staining with α-actin, cytokeratin AE1/AE3, synaptophysin, and CD31 antibodies were performed. Removal of nuclear components and preservation of biomechanical properties was confirmed. In-vivo recellularization revealed promising results in progressive angiogenesis and cell seeding of epithelium-like cells in the lining of the urethra as well as smooth muscle cells in the wall structure. In-vitro urethral regeneration revealed that cell sheet engineering was the technique of choice compared to perfusion-based technique. This study may paw the road for clinical application of acellular urethral matrix with the surrounding corpus spongiosum in urological reconstructive surgery.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Abbreviations

SEM:

Scanning electron microscopy

ECM:

Extracellular matrix

References

  1. Atala, A., et al. The potential role of tissue-engineered urethral substitution: clinical and preclinical studies. J. Tissue Eng. Regen. Med. 2015. doi:10.1002/term.2112.

    Google Scholar 

  2. Barbagli, G., et al. Bulbar urethroplasty using buccal mucosa grafts placed on the ventral, dorsal or lateral surface of the urethra: are results affected by the surgical technique? J. Urol. 174(3): 955–957, 2005; discussion 957–958.

  3. Blaschko, S. D., et al. Repeat urethroplasty after failed urethral reconstruction: outcome analysis of 130 patients. J. Urol. 188(6):2260–2264, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Brown, B. N., and S. F. Badylak. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl. Res. 163(4):268–285, 2014.

    Article  CAS  PubMed  Google Scholar 

  5. Chen, F., J. J. Yoo, and A. Atala. Acellular collagen matrix as a possible “off the shelf” biomaterial for urethral repair. Urology 54(3):407–410, 1999.

    Article  CAS  PubMed  Google Scholar 

  6. Chen, F., J. J. Yoo, and A. Atala. Experimental and clinical experience using tissue regeneration for urethral reconstruction. World J. Urol. 18(1):67–70, 2000.

    Article  CAS  PubMed  Google Scholar 

  7. Chung, Y. G., et al. Acellular bi-layer silk fibroin scaffolds support tissue regeneration in a rabbit model of onlay urethroplasty. PLoS ONE 9(3):e91592, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  8. De Filippo, R. E., et al. Penile urethra replacement with autologous cell-seeded tubularized collagen matrices. J. Tissue Eng. Regen. Med. 9(3):257–264, 2015.

    Article  PubMed  Google Scholar 

  9. Fu, Q., et al. Urethral replacement using epidermal cell-seeded tubular acellular bladder collagen matrix. BJU Int. 99(5):1162–1165, 2007.

    Article  PubMed  Google Scholar 

  10. Jia, W., et al. Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model. Biomaterials 69:45–55, 2015.

    Article  CAS  PubMed  Google Scholar 

  11. Kajbafzadeh, A. M., et al. The application of tissue-engineered preputial matrix and fibrin sealant for urethral reconstruction in rabbit model. Int. Urol. Nephrol. 46(8):1573–1580, 2014.

    Article  CAS  PubMed  Google Scholar 

  12. Korkes, F., et al. Recreational use of PDE5 inhibitors by young healthy men: recognizing this issue among medical students. J. Sex. Med. 5(10):2414–2418, 2008.

    Article  PubMed  Google Scholar 

  13. Kropp, B. P., et al. Rabbit urethral regeneration using small intestinal submucosa onlay grafts. Urology 52(1):138–142, 1998.

    Article  CAS  PubMed  Google Scholar 

  14. Laird, P. W., et al. Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 19(15):4293, 1991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. le Roux, P. J. Endoscopic urethroplasty with unseeded small intestinal submucosa collagen matrix grafts: a pilot study. J. Urol. 173(1):140–143, 2005.

    Article  PubMed  Google Scholar 

  16. Li, C. L., et al. Urethral reconstruction using bone marrow mesenchymal stem cell- and smooth muscle cell-seeded bladder acellular matrix. Transplant. Proc. 45(9):3402–3407, 2013.

    Article  CAS  PubMed  Google Scholar 

  17. Matsuura, K., et al. Cell sheet approach for tissue engineering and regenerative medicine. J. Control. Release 190:228–239, 2014.

    Article  CAS  PubMed  Google Scholar 

  18. Najar, M., et al. Mesenchymal stromal cells from the foreskin: tissue isolation, cell characterization and immunobiological properties. Cytotherapy 18(3):320–335, 2016.

    Article  CAS  PubMed  Google Scholar 

  19. Orabi, H., et al. Cell-seeded tubularized scaffolds for reconstruction of long urethral defects: a preclinical study. Eur. Urol. 63(3):531–538, 2013.

    Article  PubMed  Google Scholar 

  20. Parnigotto, P. P., et al. Experimental defect in rabbit urethra repaired with acellular aortic matrix. Urol. Res. 28(1):46–51, 2000.

    Article  CAS  PubMed  Google Scholar 

  21. Peterson, A. C., and G. D. Webster. Management of urethral stricture disease: developing options for surgical intervention. BJU Int. 94(7):971–976, 2004.

    Article  PubMed  Google Scholar 

  22. Qi, N., W. J. Li, and H. Tian. A systematic review of animal and clinical studies on the use of scaffolds for urethral repair. J. Huazhong. Univ. Sci. Technol. Med. Sci. 36(1):111–117, 2016.

    Article  CAS  PubMed  Google Scholar 

  23. Raya-Rivera, A., et al. Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Lancet 377(9772):1175–1182, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Rehder, P., et al. Hypothesis that urethral bulb (corpus spongiosum) plays an active role in male urinary continence. Adv. Urol. 2016:6054730, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ribeiro-Filho, L. A., and K. D. Sievert. Acellular matrix in urethral reconstruction. Adv. Drug Deliv. Rev. 82–83:38–46, 2015.

    Article  PubMed  Google Scholar 

  26. Sievert, K. D., and E. A. Tanagho. Organ-specific acellular matrix for reconstruction of the urinary tract. World J. Urol. 18(1):19–25, 2000.

    Article  CAS  PubMed  Google Scholar 

  27. Sinha, R. J., et al. Donor site morbidity in oral mucosa graft urethroplasty: implications of tobacco consumption. BMC Urol. 9:15, 2009.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sivaraman, B., C. A. Bashur, and A. Ramamurthi. Advances in biomimetic regeneration of elastic matrix structures. Drug Deliv. Transl. Res. 2(5):323–350, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tang, Z., and T. Okano. Recent development of temperature-responsive surfaces and their application for cell sheet engineering. Regen. Biomater. 1(1):91–102, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Xue, J. D., et al. Seeding cell approach for tissue-engineered urethral reconstruction in animal study: a systematic review and meta-analysis. Exp. Biol. Med. (Maywood) 241(13):1416–1428, 2016.

    Article  Google Scholar 

Download references

Acknowledgments

We are highly grateful from Mrs. S. Lotfi for her precise final linguistic revision of the manuscript.

Conflict of interest

No conflict of interest exists in relation to the submitted manuscript and there was no source of extra institutional commercial funding or funding received from National Institutes of Health (NIH), Wellcome Trust, Howard Hughes Medical Institute (HHMI) and others.

Author information

Authors and Affiliations

  1. Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children’s Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Gharib’s Street, Keshavarz Boulevard, Tehran, 1419433151, Iran

    Abdol-Mohammad Kajbafzadeh, Reza Abbasioun, Shabnam Sabetkish, Nastaran Sabetkish, Parvin Rahmani & Hamid Arshadi

  2. Department of Urology and Renal Transplantation, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

    Kamyar Tavakkolitabassi

Authors
  1. Abdol-Mohammad Kajbafzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reza Abbasioun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shabnam Sabetkish
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nastaran Sabetkish
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Parvin Rahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kamyar Tavakkolitabassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hamid Arshadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdol-Mohammad Kajbafzadeh.

Additional information

Associate Editor Christiani Amorim oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kajbafzadeh, AM., Abbasioun, R., Sabetkish, S. et al. Future Prospects for Human Tissue Engineered Urethra Transplantation: Decellularization and Recellularization-Based Urethra Regeneration. Ann Biomed Eng 45, 1795–1806 (2017). https://doi.org/10.1007/s10439-017-1857-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-017-1857-x

Keywords

Search

Navigation