Airway reconstruction using decellularized tracheal allografts in a porcine model (original) (raw)

Abstract

Purpose

Tracheal cartilage reconstruction is an essential approach for the treatment of tracheal congenital abnormalities or injury. Here, we evaluated the use of allogeneic decellularized tracheas as novel support scaffolds.

Methods

Six weaned pigs (4-week-old domestic males) were transplanted with allogeneic tracheal graft patches (three decellularized and three fresh tracheal scaffolds) onto artificial defects (approximately 15 × 15 mm). After 11 weeks, the tracheas were evaluated by bronchoscopy and histological studies.

Results

No pigs displayed airway symptoms during the observation period. Tracheal lumen restored by fresh graft patches showed more advanced narrowing than that treated with decellularized grafts by bronchoscopy. Histologically, fresh grafts induced typical cellular rejection; this was decreased with decellularized grafts. In addition, immunohistochemistry demonstrated regenerating foci of recipient cartilage along the adjacent surface of decellularized tracheal grafts.

Conclusion

Decellularized allogeneic tracheal scaffolds could be effective materials for restoring impaired trachea.

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References

  1. Gordin A, Chadha NK, Campisi P, Luginbuehl I, Taylor G, Forte V (2011) An animal model for endotracheal tube-related laryngeal injury using hypoxic ventilation. Otolaryngol Head Neck Surg 144(2):247–251. doi:10.1177/0194599810392894
    Article PubMed Google Scholar
  2. Monnier P (2011) Applied surgical anatomy of the larynx and trachea. In: Monnier P (ed) Pediatric airway surgery: management of laryngotracheal stenosis in infants and children. Springer, Berlin, Heidelberg, pp 7–29. doi:10.1007/978-3-642-13535-4_2
    Chapter Google Scholar
  3. Kojima K, Vacanti CA (2014) Tissue engineering in the trachea. Anat Rec (Hoboken) 297(1):44–50. doi:10.1002/ar.22799
    Article CAS Google Scholar
  4. Bogan SL, Teoh GZ, Birchall MA (2016) Tissue engineered airways: a prospects article. J Cell Biochem 117(7):1497–1505. doi:10.1002/jcb.25512
    Article CAS PubMed Google Scholar
  5. Zang M, Zhang Q, Chang EI, Mathur AB, Yu P (2013) Decellularized tracheal matrix scaffold for tracheal tissue engineering: in vivo host response. Plast Reconstr Surg 132(4):549e–559e. doi:10.1097/PRS.0b013e3182a013fc
    Article CAS PubMed Google Scholar
  6. Ehashi T, Nishigaito A, Fujisato T, Moritan Y, Yamaoka T (2011) Peripheral nerve regeneration and electrophysiological recovery with CIP-treated allogeneic acellular nerves. J Biomater Sci Polym Ed 22(4–6):627–640. doi:10.1163/092050610X488250
    Article CAS PubMed Google Scholar
  7. Mahara A, Somekawa S, Kobayashi N, Hirano Y, Kimura Y, Fujisato T, Yamaoka T (2015) Tissue-engineered acellular small diameter long-bypass grafts with neointima-inducing activity. Biomaterials 58:54–62. doi:10.1016/j.biomaterials.2015.04.031
    Article CAS PubMed Google Scholar
  8. Mahara A, Sago M, Yamaguchi H, Ehashi T, Minatoya K, Tanaka H, Nakatani T, Moritan T, Fujisato T, Yamaoka T (2015) Micro-CT evaluation of high pressure-decellularized cardiovascular tissues transplanted in rat subcutaneous accelerated-calcification model. J Artif Organs 18(2):143–150. doi:10.1007/s10047-014-0808-7
    Article CAS PubMed Google Scholar
  9. Stewart S, Fishbein MC, Snell GI, Berry GJ, Boehler A, Burke MM, Glanville A, Gould FK, Magro C, Marboe CC, McNeil KD, Reed EF, Reinsmoen NL, Scott JP, Studer SM, Tazelaar HD, Wallwork JL, Westall G, Zamora MR, Zeevi A, Yousem SA (2007) Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant 26(12):1229–1242. doi:10.1016/j.healun.2007.10.017
    Article PubMed Google Scholar
  10. Omori K, Nakamura T, Kanemaru S, Asato R, Yamashita M, Tanaka S, Magrufov A, Ito J, Shimizu Y (2005) Regenerative medicine of the trachea: the first human case. Ann Otol Rhinol Laryngol 114(6):429–433. doi:10.1177/000348940511400603
    Article PubMed Google Scholar
  11. Macchiarini P, Walles T, Biancosino C, Mertsching H (2004) First human transplantation of a bioengineered airway tissue. J Thorac Cardiovasc Surg 128(4):638–641. doi:10.1016/j.jtcvs.2004.02.042
    Article PubMed Google Scholar
  12. Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, Cogan TA, Dodson A, Martorell J, Bellini S, Parnigotto PP, Dickinson SC, Hollander AP, Mantero S, Conconi MT, Birchall MA (2008) Clinical transplantation of a tissue-engineered airway. Lancet 372(9655):2023–2030. doi:10.1016/s0140-6736(08)61598-6
    Article PubMed Google Scholar
  13. Gonfiotti A, Jaus MO, 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):238–244. doi:10.1016/S0140-6736(13)62033-4
    Article PubMed Google Scholar
  14. (2016) Macchiarini scandal is a valuable lesson for the Karolinska Institute. Nature 537(7619):137. doi:10.1038/537137a
  15. Crapo PM, Gilbert TW, Badylak SF (2011) An overview of tissue and whole organ decellularization processes. Biomaterials 32(12):3233–3243. doi:10.1016/j.biomaterials.2011.01.057
    Article CAS PubMed PubMed Central Google Scholar
  16. Shin YS, Choi JW, Park JK, Kim YS, Yang SS, Min BH, Kim CH (2015) Tissue-engineered tracheal reconstruction using mesenchymal stem cells seeded on a porcine cartilage powder scaffold. Ann Biomed Eng 43(4):1003–1013. doi:10.1007/s10439-014-1126-1
    Article PubMed Google Scholar
  17. Rutter MJ, Cotton RT, Azizkhan RG, Manning PB (2003) Slide tracheoplasty for the management of complete tracheal rings. J Pediatr Surg 38(6):928–934. doi:10.1016/s0022-3468(03)00126-x
    Article PubMed Google Scholar
  18. Provenzano MJ, Rutter MJ, von Allmen D, Manning PB, Paul Boesch R, Putnam PE, Black AP, de Alarcon A (2014) Slide tracheoplasty for the treatment of tracheoesophogeal fistulas. J Pediatr Surg 49(6):910–914. doi:10.1016/j.jpedsurg.2014.01.022
    Article PubMed Google Scholar
  19. Hung SH, Su CH, Lin SE, Tseng H (2016) Preliminary experiences in trachea scaffold tissue engineering with segmental organ decellularization. Laryngoscope 126(11):2520–2527. doi:10.1002/lary.25932
    Article CAS PubMed Google Scholar
  20. Nakayama Y, Ishibashi-Ueda H, Takamizawa K (2004) In vivo tissue-engineered small-caliber arterial graft prosthesis consisting of autologous tissue (biotube). Cell Transplant 13(4):439–449. doi:10.3727/000000004783983828
    Article PubMed Google Scholar
  21. Nakayama Y, Kaneko Y, Takewa Y, Okumura N (2016) Mechanical properties of human autologous tubular connective tissues (human biotubes) obtained from patients undergoing peritoneal dialysis. J Biomed Mater Res B Appl Biomater 104(7):1431–1437. doi:10.1002/jbm.b.33495
    Article CAS PubMed Google Scholar
  22. Satake R, Komura M, Komura H, Kodaka T, Terawaki K, Ikebukuro K, Komuro H, Yonekawa H, Hoshi K, Takato T, Nakayama Y (2016) Patch tracheoplasty in body tissue engineering using collagenous connective tissue membranes (biosheets). J Pediatr Surg 51(2):244–248. doi:10.1016/j.jpedsurg.2015.10.068
    Article PubMed Google Scholar

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Acknowledgements

We thank Mr. Minoru Ichinose and Ms. Hiroko Komura for their excellent technical assistance and Mr. Jyunpei Yamamoto for assistance with the high-pressure treatment of tissues. This work was supported by JSPS KAKENHI (Grant Numbers JP16K20348 and JP16K11359) and a Grant-in-Aid from the National Center for Child Health and Development (Grant Number 27-8).

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Authors and Affiliations

  1. Division of Surgery, Department of Surgical Specialties, National Center for Child Health and Development, Tokyo, Japan
    Michinobu Ohno
  2. Department of Pediatric Surgery, Graduate School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
    Yasushi Fuchimoto & Tatsuo Kuroda
  3. Division for Advanced Medical Sciences, National Center for Child Health and Development, Tokyo, Japan
    Huai-Che Hsu & Shin Enosawa
  4. Division of Pulmonology, Department of Medical Specialties, National Center for Child Health and Development, Tokyo, Japan
    Masataka Higuchi
  5. Department of Pediatric Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    Makoto Komura
  6. Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
    Tetsuji Yamaoka
  7. Department of Reproductive Biology, National Center for Child Health and Development, Tokyo, Japan
    Akihiro Umezawa

Authors

  1. Michinobu Ohno
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  2. Yasushi Fuchimoto
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  3. Huai-Che Hsu
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  4. Masataka Higuchi
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  5. Makoto Komura
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  6. Tetsuji Yamaoka
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  7. Akihiro Umezawa
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  8. Shin Enosawa
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  9. Tatsuo Kuroda
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Corresponding author

Correspondence toYasushi Fuchimoto.

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Human and animal rights statement

All procedures performed in studies involving animals were carried out in accordance with the ethical standards of the institution at which the studies were conducted.

Funding

This work was supported by JSPS KAKENHI (grant numbers JP16K20348 and JP16K11359) and a Grant-in-Aid from the National Center for Child Health and Development (grant number 27-8).

Conflict of interest

All authors declare that they have no conflicts of interest.

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Ohno, M., Fuchimoto, Y., Hsu, HC. et al. Airway reconstruction using decellularized tracheal allografts in a porcine model.Pediatr Surg Int 33, 1065–1071 (2017). https://doi.org/10.1007/s00383-017-4138-8

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