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The Truth Behind Esophagus: The Stem Cells’ Significance

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Digestive System Diseases

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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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.

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Authors and Affiliations

  1. First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Maximos Frountzas, Dimitrios Schizas & Theodoros Liakakos

  2. Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

    Alkistis Kapelouzou

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  1. Maximos Frountzas
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  3. Alkistis Kapelouzou
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  4. Theodoros Liakakos
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  1. Laboratory of Biology, Medical School National and Kapodistrian University of Athens, Athens, Greece

    Maria Gazouli

  2. First Department of Propaedeutic Surgery, Hippocratio General Hospital, Medical School National and Kapodistrian University of Athens, Athens, Greece

    George E. Theodoropoulos

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Frountzas, M., Schizas, D., Kapelouzou, A., Liakakos, T. (2019). The Truth Behind Esophagus: The Stem Cells’ Significance. In: Gazouli, M., Theodoropoulos, G. (eds) Digestive System Diseases. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-030-11965-2_3

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