Skip to main content
Top
Published in: Esophagus 1/2019

01-01-2019 | Original Article

Comparison of esophageal submucosal glands in experimental models for esophagus tissue engineering applications

Authors: Amulya K. Saxena, Guenther Klimbacher

Published in: Esophagus | Issue 1/2019

Login to get access

Abstract

Objective

Esophagus tissue engineering holds promises to overcome the limitations of the presently employed esophageal replacement procedures. This study investigated 5 animal models for esophageal submucosal glands (ESMG) to identify models appropriate for regenerative medicine applications. Furthermore, this study aimed to measure geometric parameters of ESMG that could be utilized for fabrication of ESMG-specific scaffolds for esophagus tissue engineering applications.

Methods

Ovine, avian, bovine, murine, and porcine esophagus were investigated using Hematoxylin–Eosin (HE), Periodic Acid Schiff (PAS), and Alcian Blue (AB), with AB applied in 3 pH levels (0.2, 1.0, and 2.5) to detect sulphated mucous. Celleye® (version F) was employed to gain parametric data on ESMGs (size, perimeter, distance to lumen, and acini concentration) necessary for scaffold fabrication.

Results

Murine, bovine, and ovine esophagus were devoid of ESMG. Avian esophagus demonstrated sulphated acid mucous producing ESMGs with a holocrine secretion pattern, whereas sulphated acid and neutral mucous producing ESMGs with a merocrine secretion pattern were observed in porcine esophagus. Distance of ESMGs to lumen ranged from 127–340 μm (avian) to 916–983 μm (porcine). ESMGs comprised 35% (avian) to 45% (porcine) area of the submucosa. ESMG had an area of 125000 μm2 (avian) to 580000 μm2 (porcine).

Conclusion

Avian and porcine esophagus possesses ESMGs. However, porcine esophagus correlates with data available on human ESMGs. Geometric and parametric data obtained from ESMG are valuable for the fabrication of ESMG-specific scaffolds for esophagus tissue engineering using the hybrid construct approach.
Literature
1.
go back to reference Clark DC. Esophageal atresia and tracheoesophageal fistula. Am Fam Phycisian. 1999;59:910–6. Clark DC. Esophageal atresia and tracheoesophageal fistula. Am Fam Phycisian. 1999;59:910–6.
3.
go back to reference Cusick EL, Batchelor AA, Spicer RD. Development of a technique for jejunal interposition in long-gap esophageal atresia. J Pediatr Surg. 1993;28:990–4.CrossRefPubMed Cusick EL, Batchelor AA, Spicer RD. Development of a technique for jejunal interposition in long-gap esophageal atresia. J Pediatr Surg. 1993;28:990–4.CrossRefPubMed
4.
go back to reference Raffensperger JG, Kuck SR, Reynolds M, et al. Intestinal bypass of the esophagus. J Pediatr Surg. 1996;31:38–46.CrossRefPubMed Raffensperger JG, Kuck SR, Reynolds M, et al. Intestinal bypass of the esophagus. J Pediatr Surg. 1996;31:38–46.CrossRefPubMed
5.
go back to reference Spitz L. Esophageal atresia- lessons I have learned in a 40-year experience. J Pediatr Surg. 2006;41:1635–40.CrossRefPubMed Spitz L. Esophageal atresia- lessons I have learned in a 40-year experience. J Pediatr Surg. 2006;41:1635–40.CrossRefPubMed
7.
go back to reference Atug O, Dobrucali A, Orlando RC. Critical pH level of lye (NaOH) for esophageal injury. Dig Dis Sci. 2009;54:980–7.CrossRefPubMed Atug O, Dobrucali A, Orlando RC. Critical pH level of lye (NaOH) for esophageal injury. Dig Dis Sci. 2009;54:980–7.CrossRefPubMed
8.
go back to reference Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2008 Annual Report of the American Association of Poison Control Center’ National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). 2009;47:911–1084.CrossRef Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2008 Annual Report of the American Association of Poison Control Center’ National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). 2009;47:911–1084.CrossRef
9.
go back to reference Saxena AK, Ackbar R, Hollwarth ME. Tissue engineering for the neonatal and pediatric patients. J Healthc Eng. 2012;3:21–52.CrossRef Saxena AK, Ackbar R, Hollwarth ME. Tissue engineering for the neonatal and pediatric patients. J Healthc Eng. 2012;3:21–52.CrossRef
10.
go back to reference Saxena AK. Tissue engineering and regenerative medicine research perspectives for pediatric surgery. Pediatr Surg Int. 2010;26:557–73.CrossRefPubMed Saxena AK. Tissue engineering and regenerative medicine research perspectives for pediatric surgery. Pediatr Surg Int. 2010;26:557–73.CrossRefPubMed
11.
go back to reference Saxena AK. Congenital anomalies of soft tissues: birth defects depending on tissue engineering solutions and present advances in regenerative medicine. Tissue Eng Part B Rev. 2010;16:455–66.CrossRefPubMed Saxena AK. Congenital anomalies of soft tissues: birth defects depending on tissue engineering solutions and present advances in regenerative medicine. Tissue Eng Part B Rev. 2010;16:455–66.CrossRefPubMed
12.
go back to reference Saxena AK. Tissue engineering: present concepts and strategies. J Ind Assoc Pediatr Surg. 2005;10:14–9.CrossRef Saxena AK. Tissue engineering: present concepts and strategies. J Ind Assoc Pediatr Surg. 2005;10:14–9.CrossRef
13.
go back to reference Saxena AK, Ainoedhofer H, Höllwarth ME. Esophagus tissue engineering: in vitro generation of esophageal epithelial cell sheets and viability on scaffold. J Pediatr Surg. 2009;44:896–901.CrossRefPubMed Saxena AK, Ainoedhofer H, Höllwarth ME. Esophagus tissue engineering: in vitro generation of esophageal epithelial cell sheets and viability on scaffold. J Pediatr Surg. 2009;44:896–901.CrossRefPubMed
14.
go back to reference Saxena AK, Kofler K, Ainödhofer H, Höllwarth ME. Esophagus tissue engineering: hybrid approach with esophageal epithelium and unidirectional smooth muscle tissue component generation in vitro. J Gastrointest Surg. 2009;13:1037–43.CrossRefPubMed Saxena AK, Kofler K, Ainödhofer H, Höllwarth ME. Esophagus tissue engineering: hybrid approach with esophageal epithelium and unidirectional smooth muscle tissue component generation in vitro. J Gastrointest Surg. 2009;13:1037–43.CrossRefPubMed
15.
go back to reference Kofler K, Leitinger G, Kristler M, Saxena AK. Smooth muscle tissue engineering for hybrid tubular organs: scanning electron microscopic investigations of cell interactions with collagen scaffolds. J Tissue Eng Regen Med. 2009;3:321–4.CrossRefPubMed Kofler K, Leitinger G, Kristler M, Saxena AK. Smooth muscle tissue engineering for hybrid tubular organs: scanning electron microscopic investigations of cell interactions with collagen scaffolds. J Tissue Eng Regen Med. 2009;3:321–4.CrossRefPubMed
16.
go back to reference Soltysiak P, Saxena AK. Micro-computed tomography for implantation site imaging during in situ oesophagus tissue engineering in a live small animal model. J Tissue Eng Regen Med. 2009;3:573–6.CrossRefPubMed Soltysiak P, Saxena AK. Micro-computed tomography for implantation site imaging during in situ oesophagus tissue engineering in a live small animal model. J Tissue Eng Regen Med. 2009;3:573–6.CrossRefPubMed
17.
go back to reference Soltysiak P, Höllwarth ME, Saxena AK. Comparisson of suture techniques in the formation of collagen scaffold tubes for composite tubular organ tissue engineering. Biomed Mater Eng. 2010;20:1–11.PubMed Soltysiak P, Höllwarth ME, Saxena AK. Comparisson of suture techniques in the formation of collagen scaffold tubes for composite tubular organ tissue engineering. Biomed Mater Eng. 2010;20:1–11.PubMed
18.
go back to reference Saxena AK, Ainoedhofer H, Höllwarth ME. Culture of ovine epithelial cells and in vitro esophagus tissue engineering. Tissue Eng Part C Methods. 2010;16:109–14.CrossRefPubMed Saxena AK, Ainoedhofer H, Höllwarth ME. Culture of ovine epithelial cells and in vitro esophagus tissue engineering. Tissue Eng Part C Methods. 2010;16:109–14.CrossRefPubMed
19.
go back to reference Kofler K, Ainoedhofer H, Tausendschön J, Höllwarth ME, Saxena AK. Esophageal smooth muscle cells dedifferentiate with loss of a-smooth muscle actin expression after 8 weeks of explant expansion in vitro culture: implications on esophagus tissue engineering. Eur Surg. 2011;43:168–73.CrossRef Kofler K, Ainoedhofer H, Tausendschön J, Höllwarth ME, Saxena AK. Esophageal smooth muscle cells dedifferentiate with loss of a-smooth muscle actin expression after 8 weeks of explant expansion in vitro culture: implications on esophagus tissue engineering. Eur Surg. 2011;43:168–73.CrossRef
20.
go back to reference Kofler K, Ainoedhofer H, Höllwarth ME, Saxena AK. Fluorescence-activated cell sorting of PCK-26 antigen-positive cells enables selection of ovine esophageal epithelial cells with improved viability on scaffolds for esophagus tissue engineering. Pediatr Surg Int. 2010;26:97–104.CrossRefPubMed Kofler K, Ainoedhofer H, Höllwarth ME, Saxena AK. Fluorescence-activated cell sorting of PCK-26 antigen-positive cells enables selection of ovine esophageal epithelial cells with improved viability on scaffolds for esophagus tissue engineering. Pediatr Surg Int. 2010;26:97–104.CrossRefPubMed
21.
go back to reference Malvasio V, Ainoedhofer H, Ackbar R, Hoellwarth ME, Saxena AK. Effects of sodium hydroxide exposure on esophageal epithelial cells in an in vitro ovine model: implications for esophagus tissue engineering. J Pediatr Surg. 2012;47:874–80.CrossRefPubMed Malvasio V, Ainoedhofer H, Ackbar R, Hoellwarth ME, Saxena AK. Effects of sodium hydroxide exposure on esophageal epithelial cells in an in vitro ovine model: implications for esophagus tissue engineering. J Pediatr Surg. 2012;47:874–80.CrossRefPubMed
22.
go back to reference Saxena AK, Baumgart H, Komann C, Ainoedhofer H, Soltysiak P, Kofler K, Höllwarth ME. Esophagus tissue engineering: in situ generation of rudimentary tubular vascularized esophageal conduit using the ovine model. J Pediatr Surg. 2010;45:859–64.CrossRefPubMed Saxena AK, Baumgart H, Komann C, Ainoedhofer H, Soltysiak P, Kofler K, Höllwarth ME. Esophagus tissue engineering: in situ generation of rudimentary tubular vascularized esophageal conduit using the ovine model. J Pediatr Surg. 2010;45:859–64.CrossRefPubMed
23.
go back to reference Macheiner T, Ackbar R, Saxena AK. Isolation, identification and culture of myenteric plexus cells from ovine esophagus. Esophagus. 2013;10:144–8.CrossRef Macheiner T, Ackbar R, Saxena AK. Isolation, identification and culture of myenteric plexus cells from ovine esophagus. Esophagus. 2013;10:144–8.CrossRef
24.
go back to reference Ackbar R, Ainoedhofer H, Gugatschka M, Saxena AK. Decellularized ovine esophageal mucosa for esophageal tissue engineering. Technol Health Care. 2012;20:215–23.PubMed Ackbar R, Ainoedhofer H, Gugatschka M, Saxena AK. Decellularized ovine esophageal mucosa for esophageal tissue engineering. Technol Health Care. 2012;20:215–23.PubMed
25.
go back to reference Saxena AK, Faraj KA, Damen WF, van Kuppevelt TH, Weijnen R, Ainoedhofer H, Höllwarth ME. Comparison of collagen scaffolds tubes for possible esophagus organ tissue engineering applications: in-situ omental implantation study in an ovine model. Eur Surg. 2010;42:309–13.CrossRef Saxena AK, Faraj KA, Damen WF, van Kuppevelt TH, Weijnen R, Ainoedhofer H, Höllwarth ME. Comparison of collagen scaffolds tubes for possible esophagus organ tissue engineering applications: in-situ omental implantation study in an ovine model. Eur Surg. 2010;42:309–13.CrossRef
26.
go back to reference Abdulnour-Nakhoul S, Nakhoul NL, Wheeler SA, Wang P, Swenson ER, Orlando RC. HCO3-secretion in the esophageal submucosal glands. Am J Physiol Gastrointest Liver Physiol. 2005;288:G736–44.CrossRefPubMed Abdulnour-Nakhoul S, Nakhoul NL, Wheeler SA, Wang P, Swenson ER, Orlando RC. HCO3-secretion in the esophageal submucosal glands. Am J Physiol Gastrointest Liver Physiol. 2005;288:G736–44.CrossRefPubMed
27.
go back to reference Christie KN, Thomson C, Hopwood D. A comparison of membrane enzymes of human and pig oesophagus; the pig oesophagus is a good model for studies of the gullet in man. Histochem J. 1995;27:231–9.CrossRefPubMed Christie KN, Thomson C, Hopwood D. A comparison of membrane enzymes of human and pig oesophagus; the pig oesophagus is a good model for studies of the gullet in man. Histochem J. 1995;27:231–9.CrossRefPubMed
28.
go back to reference Hopwood D, Coghill G, Sanders DS. Human oesophageal submucosal glands. Their detection mucin, enzyme and secretory protein content. Histochemistry. 1986;86:107–12.CrossRefPubMed Hopwood D, Coghill G, Sanders DS. Human oesophageal submucosal glands. Their detection mucin, enzyme and secretory protein content. Histochemistry. 1986;86:107–12.CrossRefPubMed
29.
go back to reference Long JD, Orlando RC. Esophageal submucosal glands: structure and function. Am J Gastroenterol. 1999;94:2818–24.CrossRefPubMed Long JD, Orlando RC. Esophageal submucosal glands: structure and function. Am J Gastroenterol. 1999;94:2818–24.CrossRefPubMed
30.
go back to reference Deinhofer MG (2008) Anatomie von Schaf und Ziege. Österreichischer Bundesverband für Schafe und Ziegen, Vienna 1–20 Deinhofer MG (2008) Anatomie von Schaf und Ziege. Österreichischer Bundesverband für Schafe und Ziegen, Vienna 1–20
31.
go back to reference Pastor LM, Ballesta J, Madrid JF, Perez-Tomas R, Hernandez F. A histochemical study of the mucins in the digestive tract of the chicken. Acta Histochem. 1988;83:91–7.CrossRefPubMed Pastor LM, Ballesta J, Madrid JF, Perez-Tomas R, Hernandez F. A histochemical study of the mucins in the digestive tract of the chicken. Acta Histochem. 1988;83:91–7.CrossRefPubMed
32.
go back to reference Dixon J, Strugala V, Griffin SM, Welfare MR, Dettmar PW, Allen A, Pearson JP. Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett’s esophagus. Am J Gastroenterol. 2001;96:2575–83.CrossRefPubMed Dixon J, Strugala V, Griffin SM, Welfare MR, Dettmar PW, Allen A, Pearson JP. Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett’s esophagus. Am J Gastroenterol. 2001;96:2575–83.CrossRefPubMed
33.
go back to reference Hamilton B, Orlando R. In vivo alkaline secretion by mammalian esophagus. Gastroenterology. 1989;97:640–8.CrossRefPubMed Hamilton B, Orlando R. In vivo alkaline secretion by mammalian esophagus. Gastroenterology. 1989;97:640–8.CrossRefPubMed
34.
go back to reference Arul GS, Moorghen M, Myerscough N, Alderson DA, Spicer RD, Corfield AP. Mucin gene expression in Barretts oesophagus: an in situ hybridisation and immunohistochemical study. Gut. 2000;47:753–61.CrossRefPubMedPubMedCentral Arul GS, Moorghen M, Myerscough N, Alderson DA, Spicer RD, Corfield AP. Mucin gene expression in Barretts oesophagus: an in situ hybridisation and immunohistochemical study. Gut. 2000;47:753–61.CrossRefPubMedPubMedCentral
35.
go back to reference Shibata T, Imai M, Moroguchi K, Takada Y, Hayama H. Actual characteristics of the glands distributed in the lamina propria mucosae of the fowl esophagus. Okajimas Folia Anat Jpn. 1991;68:41–5.CrossRefPubMed Shibata T, Imai M, Moroguchi K, Takada Y, Hayama H. Actual characteristics of the glands distributed in the lamina propria mucosae of the fowl esophagus. Okajimas Folia Anat Jpn. 1991;68:41–5.CrossRefPubMed
Metadata
Title
Comparison of esophageal submucosal glands in experimental models for esophagus tissue engineering applications
Authors
Amulya K. Saxena
Guenther Klimbacher
Publication date
01-01-2019
Publisher
Springer Singapore
Published in
Esophagus / Issue 1/2019
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-018-0633-9

Other articles of this Issue 1/2019

Esophagus 1/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.