Stem Cell Reviews and Reports

, Volume 11, Issue 2, pp 347–356 | Cite as

In Vivo Tissue-Engineered Allogenic Trachea Transplantation in Rabbits: A Preliminary Report

  • Aysegul Batioglu-KaraaltinEmail author
  • Mehmet Veli Karaaltin
  • Ercument Ovali
  • Ozgur Yigit
  • Merve Kongur
  • Oznur Inan
  • Erol Bozkurt
  • Harun Cansiz


Conventional tracheal reconstruction techniques are not successful at restoring functional units in situations with extensive damage involving more than half the length of the trachea. For the first time, we investigated in vivo tissue-engineered trachea regeneration from a decellularized cadaveric trachea matrix with seeded adult adipose tissue-derived mesenchymal stem cells (MSCs) and investigated the integration of the matrix into the recipient tracheal side. For the procedure, 1.8-cm grafts were prepared from 3.5-cm tracheas of three donor rabbits. Then, tracheal grafts were rendered nonimmunogenic using a decellularization technique. MSCs isolated from recipient rabbit adipose tissue were cultured and marked before being seeded in the decellularized matrix. A total of 1.8 cm of the recipient tracheas was replaced with either a decellularized tracheal matrix (group 1) or tracheal matrix-seeded MSCs (group 2). Rabbits survived 17 ± 2 days in the first group, and the causes of death were separation in the anastomosis region, airway obstruction, and infection. In the second group, animals were sacrificed on the 30th, 60th, and 90th days of follow-up. Histopathological analysis revealed the integration of MSCs seeded-decellularized cadaveric tracheas to the recipient tracheal sides and increased angiogenesis. The MSCs were traced by fluorescence microscopy in the ciliated epithelium, under the epithelium, and in the cartilage of the integrated new trachea. Tracheas generated by autologous cells and tissue-engineering techniques will be a great source for the treatment of life-threatening tracheal injuries after the completion of related studies.


Trachea Adipose tissue-derived mesenchymal stem cell Tissue engineering 


Oral Presentation

34th National ENT & Head & Neck Surgery Congress (10-14 October 2012, Rixos Sungate-Antalya)

Conflicts of Interest

The authors indicate no potential conflicts of interest.


  1. 1.
    Grillo, H. C. (2002). Tracheal replacement: a critical review. Ann Thorac Surg, 73, 1995–2004.CrossRefPubMedGoogle Scholar
  2. 2.
    Olson, J. L., Atala, A., & Yoo, J. J. (2011). Tissue engineering: current strategies and future directions. Chonnam Med J, 47, 1–13.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Bang, O. Y., Lee, J. S., Lee, P. H., & Lee, G. (2005). Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol, 57, 874.CrossRefPubMedGoogle Scholar
  4. 4.
    Herrera, M. B., Bussolati, B., Bruno, S., Fonsato, V., Romanazzi, G. M., & Camussi, G. (2004). Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med, 14, 1035.PubMedGoogle Scholar
  5. 5.
    Prockop, D. J. (1997). Marrow stem cells as stem cells for nonhematopoietic tissues. Science, 276, 71–74.CrossRefPubMedGoogle Scholar
  6. 6.
    Minguell, J. J., Erices, A., & Conget, P. (2003). Mesenchymal stem cells. Exp Biol Med, 226, 507–520.Google Scholar
  7. 7.
    Noth, U., Tuli, R., Osyczka, A. M., Danielson, K. G., & Tuan, R. S. (2002). In vitro engineered cartilage constructs produced by presscoating biodegradable polymer with human mesenchymal stem cells. Tissue Eng, 8, 131–144.CrossRefPubMedGoogle Scholar
  8. 8.
    Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, M. A., et al. (2008). Clinical transplantation of a tissue-engineered airway. Lancet, 372, 2023–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Go, T., Jungebluth, P., Baiguero, S., Asnaghi, A., Martorell, J., et al. (2010). Both epithelial cells and mesenchymal stem cell–derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. J Thorac Cardiovasc Surg, 139, 437–43.CrossRefPubMedGoogle Scholar
  10. 10.
    Jungebluth, P1., Bader, A., Baiguera, S., Möller, S., Jaus, M., et al. (2012). The concept of in vivo airway tissue engineering. Biomaterials, 33(17), 4319–26.CrossRefPubMedGoogle Scholar
  11. 11.
    Suzuki, T., Kobayashi, K., Tada, Y., & Suzuki, Y. (2008). Regeneration of the trachea using a bioengineered scaffold with adipose-derived stem cells. Ann Otol Rhinol Laryngol, 117(6), 453–463.CrossRefPubMedGoogle Scholar
  12. 12.
    Okano, W. MD, Nomoto, Y. MD, & Wada, I. MD. (2009). Kobayashi bioengineered trachea with fibroblasts in a rabbit model. Ken Ann Otol Rhinol Laryngol, 118(11), 796–804.Google Scholar
  13. 13.
    Karlen, Y., McNair, A., Perseguers, S., Mazza, C., & Mermod, N. (2007). Statisticalsignificance of quantitative PCR. BMC Bioinformatics, 8, 131.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Elliott, M. J., Haw, M. P., Jacobs, J. P., Bailey, C. M., Evans, J. N., & Herberhold, C. (1996). Tracheal reconstruction in children using cadaveric homograft trachea. Eur J Cardiothorac Surg, 10, 707–712.CrossRefPubMedGoogle Scholar
  15. 15.
    Delaere, P., Vranckx, J., Verleden, G., De Leyn, P., & Van Raemdonck, D. (2010). Tracheal allotransplantation after withdrawal of immunosuppressive therapy. N Engl J Med, 362, 138–145.CrossRefPubMedGoogle Scholar
  16. 16.
    Li, J., Xu, P., & Chen, H. (1997). Successful tracheal autotransplantation with two-stage approach using the greater omentum. Ann Thorac Surg, 64(1), 199–202.CrossRefPubMedGoogle Scholar
  17. 17.
    Klepetko, W., Marta, G. M., Wisser, W., & Melis, E. (2004). Heterotopic tracheal transplantation with omentum wrapping in the abdominal position preserves functional and structural integrity of a human tracheal allograft. J Thorac Cardiovasc Surg, 127, 862–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Elliott, M. J1., De Coppi, P., Speggiorin, S., Roebuck, D., Butler, C. R., et al. (2012). Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study. Lancet, 380(9846), 994–1000.CrossRefPubMedGoogle Scholar
  19. 19.
    Gonfiotti, A., Jaus, M. O., Barale, D., Baiguera, S., Comin, C., Lavorini, F., Fontana, G., Sibila, O., Rombolà, G., Jungebluth, P., & Macchiarini, P. (2014). The first tissue-engineered airway transplantation: 5-year follow-up results. Lancet, 383(9913), 238–44.CrossRefPubMedGoogle Scholar
  20. 20.
    Kojima, K., Bonassar, L. J., Roy, A. K., Vacanti, C. A., & Cortiella, J. (2002). Autologous tissue-engineered trachea with sheep nasal chondrocytes. J Thorac Cardiovasc Surg, 123, 1177–1184.CrossRefPubMedGoogle Scholar
  21. 21.
    Wu, W., Feng, X., Mao, T., Feng, X., Ouyang, H. W., Zhao, G., et al. (2007). Engineering of human tracheal tissue with collagenen forced poly-lactic-glycolic acid non-woven mesh: a preliminary study in nude mice. Br J Oral Maxillofac Surg, 45, 272–278.CrossRefPubMedGoogle Scholar
  22. 22.
    Kim, D. Y., Pyun, J. H., Choi, J. W., Kim, J. H., Lee, J. S., Shin, H. A., et al. (2010). Tissue-engineered allograft tracheal cartilage using fibrin/ hyaluronan composite gel and its in vivo implantation. Laryngoscope, 120, 30–38.CrossRefPubMedGoogle Scholar
  23. 23.
    Kafienah, W., Mistry, S., Williams, C., & Hollander, A. P. (2006). Nucleostemin is a marker of proliferating stromal stem cells in adult human bone marrow. Stem Cells, 24, 113–120.CrossRefGoogle Scholar
  24. 24.
    Tsutsumi, S., Shimazu, A., Miyazaki, K., Pan, H., Koike, C., Yoshida, E., et al. (2001). Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun, 288(2), 413–419.CrossRefPubMedGoogle Scholar
  25. 25.
    Bianchi, G., Banfi, A., Mastrogiacomo, M., Notaro, R., Luzzatto, L., Cancedda, R., et al. (2003). Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Exp Cell Res, 287, 98–105.CrossRefPubMedGoogle Scholar
  26. 26.
    Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.CrossRefPubMedGoogle Scholar
  27. 27.
    Singer, N. G., & Caplan, A. I. (2011). Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol, 6, 457–478.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Aysegul Batioglu-Karaaltin
    • 1
    Email author
  • Mehmet Veli Karaaltin
    • 2
  • Ercument Ovali
    • 3
  • Ozgur Yigit
    • 4
  • Merve Kongur
    • 3
  • Oznur Inan
    • 5
  • Erol Bozkurt
    • 6
  • Harun Cansiz
    • 1
  1. 1.Department of Otolaryngology Head and Neck SurgeryIstanbul University Cerrahpasa Medicine FacultyFatihTurkey
  2. 2.Department of Plastic and Reconstructive SurgeryAcibadem University Medicine FacultyIstanbulTurkey
  3. 3.Acibadem Labcell LaboratoriesIstanbulTurkey
  4. 4.Department of Otolaryngology Head and Neck SurgeryIstanbul Education and Research HospitalIstanbulTurkey
  5. 5.Experimental Research Center of Bezmialem UniversityIstanbulTurkey
  6. 6.Department of PathologyIstanbul Education and Research HospitalIstanbulTurkey

Personalised recommendations