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The Truth Behind Esophagus: The Stem Cells’ Significance

  • Maximos Frountzas
  • Dimitrios Schizas
  • Alkistis Kapelouzou
  • Theodoros Liakakos
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

The presence of a continuously renewing squamous cell epithelium that covers the esophagus demonstrates the crucial role of a pluripotent stem cell population that regulates esophageal homeostasis and pathogenesis of the most esophageal diseases. Esophageal development and maintenance of adult esophageal homeostasis share common mechanisms, as transformation of early columnar esophageal epithelium into mature squamous epithelial cells is based on molecular regulators such as SOX2, p63, Notch, and NANOG, which are also present in fetal esophageal development. In addition, esophageal cancer seems to be associated with the cancer stem cell hypothesis, which refers to mutated pluripotent stem cell populations that give rise to cancerous cell accumulations. These mutations have been related to stem cell markers like aldehyde dehydrogenase-1 (ALDH1), Lgr5, Wnt/β-catenin, Notch, CD44, and CD177. Dietary habits, like alcohol consumption, and caustic injury of the esophagus have been correlated to such mutations and consequent carcinogenesis. Moreover, Barrett’s esophagus due to gastroesophageal reflux disease (GERD), which is a precancerous lesion that leads to esophageal adenocarcinoma, rises from either a native squamous esophageal stem cell population that turns into intestinal epithelial cell (transdifferentiation) or an intestinal esophageal stem cell population derived from the esophagus, stomach, or circulation (transcommitment), which turns immortal due to mutations in the stem cell markers Sox9, Sox2, p63, Cdx1, Cdx2, and Foxa2. Nevertheless, esophageal cancer stem cell-regulating molecules could be ideal pharmaceutic targets for future therapeutic attempts against esophageal cancer. Furthermore, stem cell technology could enhance tissue-engineering esophageal scaffolds in order to replace damaged esophageal segments with transplanted artificial segments, after radical surgical operations due to esophageal cancer, massive esophageal caustic injury, endoscopic esophageal dissection due to Barrett’s esophagus, ionizing radiation, and pediatric diseases, such as esophageal atresia or tracheoesophageal fistula.

Keywords

Esophagus Stem Cell Barrett Scaffold 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maximos Frountzas
    • 1
  • Dimitrios Schizas
    • 1
  • Alkistis Kapelouzou
    • 2
  • Theodoros Liakakos
    • 1
  1. 1.First Department of Surgery, Laikon General Hospital, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  2. 2.Center for Clinical, Experimental Surgery and Translational ResearchBiomedical Research Foundation of the Academy of AthensAthensGreece

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