In-vivo trachea regeneration: fabrication of a tissue-engineered trachea in nude mice using the body as a natural bioreactor | springermedicine.com

Springer Medicine

Top

Published in:

01-08-2015 | Original Article

In-vivo trachea regeneration: fabrication of a tissue-engineered trachea in nude mice using the body as a natural bioreactor

Authors: Abdol-Mohammad Kajbafzadeh, Shabnam Sabetkish, Nastaran Sabetkish, Samad Muhammadnejad, Aram Akbarzadeh, Seyyed Mohammad Tavangar, Mohammad Javad Mohseni, Saeid Amanpour

Published in: Surgery Today | Issue 8/2015

Login to get access

Abstract

Purpose

To investigate the outcomes of implanting rat decellularized trachea scaffold (DTS) between the paravertebral muscles of nude mice using the body as a bioreactor for total graft recellularization.

Methods

The tracheas of four rats were aseptically resected and decellularized. To assess the efficiency of the decellularization procedure, all decellularized scaffolds and native control tissues were evaluated with scanning electron microscopy (SEM), DAPI staining, DNA quantification, biomechanical analyses and hydroxyproline measurement. They were then implanted between the paravertebral muscles of four nude mice. The biopsies were precisely evaluated at 1, 3, 6 and 12 months postoperatively for tracheal cartilage and soft tissue recellularization by staining for TTF1, CD34, S100 and leukocyte common antibody.

Results

Hematoxylin and eosin (H&E) staining, SEM and the tensile test confirmed the preservation of the tissue structure and the biophysical and biochemical properties of the DTS. The present study clearly demonstrated that the hydroxyproline content of the DTS was similar to that of the native tissue. On the other hand, in biopsy samples obtained after 12 months, histological evaluation showed superior organization and cell seeding in both the cartilage and connective tissues.

Conclusion

This study demonstrated the feasibility of using a natural bioreactor for recellularizing DTS; this may have the potential to facilitate homologous transplantation for repairing segmental trachea defects.

1.

Remlinger NT, Czajka CA, Juhas ME, Vorp DA, Stolz DB, Badylak SF, et al. Hydrated xenogeneic decellularized tracheal matrix as a scaffold for tracheal reconstruction. Biomaterials. 2010;31(13):3520–6.PubMedCrossRef

2.

Wright CD, Grillo HC, Wain JC, Wong DR, Donahue DM, Gaissert HA, et al. Anastomotic complications after tracheal resection: prognostic factors and management. J Thorac Cardiovasc Surg. 2004;128(5):731.PubMedCrossRef

3.

Cotton R. Management of subglottic stenosis in infancy and childhood. Review of a consecutive series of cases managed by surgical reconstruction. Ann Otol Rhinol Laryngol. 1978;87(5 pt 1):649.PubMedCrossRef

4.

Macchiarini P, Chapelier A, Lenot B, Cerrina J, Dartevelle P. Laryngotracheal resection and reconstruction for postintubation subglottic stenosis: lessons learned. Eur J Cardiothorac Surg. 1993;7(6):300–5.PubMedCrossRef

5.

Wright CD, Graham BB, Grillo HC, Wain JC, Mathisen DJ. Pediatric tracheal surgery. Ann Thorac Surg. 2002;74(2):308–14.PubMedCrossRef

6.

Grillo HC. Tracheal replacement: a critical review. Ann Thorac Surg. 2002;73(6):1995–2004.PubMedCrossRef

7.

Okumus A, Kabakas F, Kuvat SV, Bilir A, Aydin A. Circumferential trachea reconstruction with a prefabricated axial bio-synthetic flap: experimental study. Int J Pediatr Otorhinolaryngol. 2005;69(3):335–44.PubMedCrossRef

8.

Grimmer JF, Gunnlaugsson CB, Alsberg E, Murphy HS, Kong HJ, Mooney DJ, et al. Tracheal reconstruction using tissue-engineered cartilage. Arch Otolaryngol Head Neck Surg. 2004;130(10):1191.PubMedCrossRef

9.

Baiguera S, Jungebluth P, Burns A, Mavilia C, Haag J, De Coppi P et al. Tissue engineered human tracheas for in vivo implantation. Biomaterials. 2010;31(34):8931–8.PubMedCrossRef

10.

Bader A, Macchiarini P. Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach. J Cell Mol Med. 2010;14(7):1877–89.PubMedCentralPubMedCrossRef

11.

Brown BN, Valentin JE, Stewart-Akers AM, McCabe GP, Badylak SF. Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials. 2009;30(8):1482–91.PubMedCentralPubMedCrossRef

12.

Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32(12):3233–43.PubMedCentralPubMedCrossRef

13.

Zheng M, Chen J, Kirilak Y, Willers C, Xu J, Wood D. Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation. J Biomed Mater Res B Appl Biomater. 2005;73(1):61–7.PubMedCrossRef

14.

Woessner J. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961;93(2):440–7.PubMedCrossRef

15.

Nakanishi R, Shirakusa T, Mitsudomi T. Maximum length of tracheal autografts in dogs. J Thorac Cardiovasc Surg. 1993;106(6):1081.PubMed

16.

Cavadas PC. Tracheal reconstruction using a free jejunal flap with cartilage skeleton: experimental study. Plast Reconstr Surg. 1998;101(4):937.PubMedCrossRef

17.

Cull DL, Lally KP, Mair EA, Daidone M, Parsons DS. Tracheal reconstruction with polytetrafluoroethylene graft in dogs. Ann Thorac Surg. 1990;50(6):899–901.PubMedCrossRef

18.

Teramachi M, Nakamura T, Yamamoto Y, Kiyotani T, Takimoto Y, Shimizu Y. Porous-type tracheal prosthesis sealed with collagen sponge. Ann Thorac Surg. 1997;64(4):965–9.PubMedCrossRef

19.

Deslauriers J, Ginsberg R, Nelems J, Pearson F. Innominate artery rupture: a major complication of tracheal surgery. Ann Thorac Surg. 1975;20(6):671–7.PubMedCrossRef

20.

Lenot B, Macchiarini P, Dulmet E, Weiss M, Dartevelle P. Tracheal allograft replacement: an unsuccessful method. Eur J Cardiothorac Surg. 1993;7(12):648–52.PubMedCrossRef

21.

Carbognani P, Spaggiari L, Solli P, Corradi A, Cantoni AM, Barocelli E, et al. Experimental tracheal transplantation using a cryopreserved aortic allograft. Eur Surg Res. 1999;31(2):210–5.PubMedCrossRef

22.

Kojji K. Tissue engineered trachea using decellularized aorta. J Bioeng Biomed Sci. 2011.

23.

Grillo H, Dignan E, Miura T. Experimental reconstruction of cervical trachea after circumferential resection. Plast Reconstr Surg. 1966;38(3):272.CrossRef

24.

Kato R, Onuki AS, Watanabe M, Hashizume T, Kawamura M, Kikuchi K, et al. Tracheal reconstruction by esophageal interposition: an experimental study. Ann Thorac Surg. 1990;49(6):951–4.PubMedCrossRef

25.

Letang E, Sanchez-Lloret J, Gimferrer J, Ramirez J, Vicens A. Experimental reconstruction of the canine trachea with a free revascularized small bowel graft. Ann Thorac Surg. 1990;49(6):955–8.PubMedCrossRef

26.

Vacanti CA, Paige KT, Kim WS, Sakata J, Upton J, Vacanti JP. Experimental tracheal replacement using tissue-engineered cartilage. J Pediatr Surg. 1994;29(2):201–5.PubMedCrossRef

27.

Sakata J, Vacanti C, Schloo B, Healy G, Langer R, Vacanti J. Tracheal composites tissue engineered from chondrocytes, tracheal epithelial cells, and synthetic degradable scaffolding. 1994. London: Elsevier.

28.

Elliott MJ, De Coppi P, Speggiorin S, Roebuck D, Butler CR, Samuel E et al. Stem-cell-based tissue engineered trachea replacement in a child: a 2-year follow-up study. Lancet. 2012;380(9846):994–1000.PubMedCentralPubMedCrossRef

29.

Macchiarini P, Jungebluth P, Go T, Asnaghi M, Rees LE, Cogan TA, et al. Clinical transplantation of a tissue-engineered airway. Lancet. 2008;372(9655):2023–30.PubMedCrossRef

30.

Jungebluth P, Go T, Asnaghi A, Bellini S, Martorell J, Calore C, et al. Structural and morphologic evaluation of a novel detergent-enzymatic tissue-engineered tracheal tubular matrix. J Thorac Cardiovasc Surg. 2009;138(3):586.PubMedCrossRef

31.

Baiguera S, Del Gaudio C, Jaus MO, Polizzi L, Gonfiotti A, Comin CE et al. Long-term changes to in vitro preserved bioengineered human trachea and their implications for decellularized tissues. Biomaterials. 2012;33(14):3662–72.PubMedCrossRef

32.

Go T, Jungebluth P, Baiguero S, Asnaghi A, Martorell J, Ostertag H, et al. Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. J Thorac Cardiovasc Surg. 2010;139(2):437–43.PubMedCrossRef

33.

Jungebluth P, Bader A, Baiguera S, Moller S, Jaus M, Lim ML, et al. The concept of in vivo airway tissue engineering. Biomaterials. 2012;33(17):4319–26.PubMedCrossRef

34.

Kojima K, Ignotz RA, Kushibiki T, Tinsley KW, Tabata Y, Vacanti CA. Tissue-engineered trachea from sheep marrow stromal cells with transforming growth factor [beta] 2 released from biodegradable microspheres in a nude rat recipient. J Thorac Cardiovasc Surg. 2004;128(1):147–53.PubMedCrossRef

35.

Sekine T, Nakamura T, Liu Y, Ueda H, Matsumoto K, Shimizu Y. Collagen coated Y-shaped prosthesis for cardinal replacement promotes regeneration of the tracheal epithelium. ASAIO J. 2000;46(4):421.PubMedCrossRef

36.

Baiguera S, Gonfiotti A, Jaus M, Comin CE, Paglierani M, Del Gaudio C et al. Development of bioengineered human larynx. Biomaterials. 2011;32(19):4433–42.PubMedCrossRef

37.

Curcio E, Macchiarini P, De Bartolo L. Oxygen mass transfer in a human tissue-engineered trachea. Biomaterials. 2010;31(19):5131–6.PubMedCrossRef

38.

Haag J, Baiguera S, Jungebluth P, Barale D, Del Gaudio C, Castiglione F et al. Biomechanical and angiogenic properties of tissue-engineered rat trachea using genipin cross-linked decellularized tissue. Biomaterials. 2011.

39.

Walles T, Herden T, Haverich A, Mertsching H. Influence of scaffold thickness and scaffold composition on bioartificial graft survival. Biomaterials. 2003;24(7):1233–9.PubMedCrossRef

Title: In-vivo trachea regeneration: fabrication of a tissue-engineered trachea in nude mice using the body as a natural bioreactor
Authors: Abdol-Mohammad Kajbafzadeh
Shabnam Sabetkish
Nastaran Sabetkish
Samad Muhammadnejad
Aram Akbarzadeh
Seyyed Mohammad Tavangar
Mohammad Javad Mohseni
Saeid Amanpour
Publication date: 01-08-2015
Publisher: Springer Japan
Published in: Surgery Today / Issue 8/2015
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI: https://doi.org/10.1007/s00595-014-0993-2

Home
Congress Coverage
Clinical Collections
- Advances in Alzheimer’s
About Springer Medicine
Key Specialties