Regeneration of the Gastric Mucosa and its Glands from Stem Cells

Werner      Hoffmann

Abstract

Mucous epithelia and their glands represent vital surfaces of the body which are topologically in direct contact and communicate with the environment. These highly specialized epithelia are protected by several lines of defence, such as mucous gels, regeneration and repair mechanisms, and acute inflammatory processes. Pathologically, chronic inflammation is associated with cancer. There are two different regeneration and repair mechanisms of mucous epithelia known which also cover different time scales. First, rapid repair of superficial lesions via cell migration - a process called restitution - starts within minutes. Second, continuous regeneration via differentiation and proliferation of stem and progenitor cells is responsible for self-renewal within days to months. This article reviews molecular mechanisms responsible for the regeneration of various mucous epithelia with a special emphasis on the complex situation in the gastric mucosa and its glands. For example, the two gross types of gastric units, i.e., the fundic and the antral types, respectively, differ largely by their histology, regeneration rates and regeneration profiles. Currently, a rough picture is emerging on the molecular mechanisms behind including the characterization of different somatic stem cell types and stem cell signaling pathways. Furthermore, dysregulated regeneration is well known now as a cause of various metaplasias (reversible remodeling of epithelia) and cancer, with chronic inflammation playing a key role. Understanding the molecular mechanisms of regeneration and their dysregulation is essential for the development of new strategies for cancer prevention and therapy and it will also promote the emerging field of regenerative medicine and tissue engineering.

Keywords: Gastric mucosa, regenerative medicine, stem cells, regeneration, gastric cancer, intestinal metaplasia, SPEM, trefoil factors