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

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Abstract

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.

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References

  1. Grillo, H. C. (2002). Tracheal replacement: a critical review. Ann Thorac Surg, 73, 1995–2004.

    Article  PubMed  Google Scholar 

  2. Olson, J. L., Atala, A., & Yoo, J. J. (2011). Tissue engineering: current strategies and future directions. Chonnam Med J, 47, 1–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  5. Prockop, D. J. (1997). Marrow stem cells as stem cells for nonhematopoietic tissues. Science, 276, 71–74.

    Article  CAS  PubMed  Google Scholar 

  6. Minguell, J. J., Erices, A., & Conget, P. (2003). Mesenchymal stem cells. Exp Biol Med, 226, 507–520.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  8. Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, M. A., et al. (2008). Clinical transplantation of a tissue-engineered airway. Lancet, 372, 2023–30.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. Karlen, Y., McNair, A., Perseguers, S., Mazza, C., & Mermod, N. (2007). Statisticalsignificance of quantitative PCR. BMC Bioinformatics, 8, 131.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  27. Singer, N. G., & Caplan, A. I. (2011). Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol, 6, 457–478.

    Article  CAS  PubMed  Google Scholar 

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Oral Presentation

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

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Correspondence to Aysegul Batioglu-Karaaltin.

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Batioglu-Karaaltin, A., Karaaltin, M.V., Ovali, E. et al. In Vivo Tissue-Engineered Allogenic Trachea Transplantation in Rabbits: A Preliminary Report. Stem Cell Rev and Rep 11, 347–356 (2015). https://doi.org/10.1007/s12015-014-9570-8

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  • DOI: https://doi.org/10.1007/s12015-014-9570-8

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