In the human body the gastrointestinal (GI) tract is lined with mucosal tissues or mucosa. As shown in Figure 7.0.1, mucosa is primarily comprised of epithelial cells that are attached to the basement membrane. Protruding from the wall of the intestine are tiny, finger-like projections called villi that increase the absorptive area and the surface area of the intestinal wall. Digested nutrients (including sugars and amino acids) pass into the villi through diffusion. Circulating blood then carries these nutrients away. Unlike the mucosal tissue of the inner surface of the eyelids or the mouth, the epithelial cells which line the inside of the stomach are exposed to much harsher conditions, e.g., acid (i.e., hydrochloric acid), sometimes alcohol, enzymes (e.g., pepsin) for digesting food and waste generated therefrom. Mucous secretion essentially protects the cells on the inside of the stomach and duodenum from damage by acid or enzymes, for example by presenting bicarbonate to neutralize some of the effects of acid on the stomach's inner lining, as well as inhibitors to block the enzymatic activity. Once the mucous secretions of the epithelial cells stop, the inner lining of the stomach or duodenum would eventually be eroded by the combined action of acid and enzymes, leading to ulcer.
An ulcer is a deep defect in the esophageal, gastric, duodenal or intestinal wall involving the entire mucosal thickness and penetrating through the muscular mucosae. Figure 7.0.2a shows a photomicrograph of gastric ulcer and its two major components involved in healing: ulcer margin and granulation tissue. Tarnawski et al. (1990) ¡°Healed experimental gastric ulcers remain histologically and ultrastructurally abnormal¡± J. Clin. Gastroenterol. 12(Suppl 1):139-147. It has been generally recognized that ulcer healing, a genetically programmed repair process, includes inflammation, cell proliferation, reepithelialization, formation of granulation tissue, angiogenesis, interactions between various cells and the matrix and tissue remodeling, all resulting in scar formation. See review by Tarnawski (2005) ¡°Cellular and molecular mechanisms of gastro-intestinal ulcer healing¡± Digestive Disease & Science 50: Sup. 1 S24-S33. Figure 7.0.2b shows a photomicrograph of gastric mucosa from the area of macroscopically healed ulcers with scar. Studies demonstrated that reepithelialized mucosa of grossly ¡°healed¡± experimental gastric ulcers has prominent histologic and ultrastructural abnormalities: reduced height, marked dilation of gastric glands, increased connective tissue, a disorganized microvascular network and increased capillary permeability. Tarnawski et al. (1990), supra. These prominent abnormalities may interfere with mucosal defense and cause ulcer recurrence when ulcerogenic factors are present. Therefore, the quality of mucosal structural restoration may be the most important factor in the determining future ulcer recurrence. Tarnawski et al. (2005), supra.
1. Regeneration of Human GI Tract without Scar Formation
2. Restoration of GI Tract of Aged Humans
3. Cloning of Gastrointestinal Villi in Cell Culture from Single, Isolated Cells
4. Regeneration of Excised Gastrointestinal Villi in GI Tissue Explants