Regenerative medicine for the upper gastrointestinal tract

The main surgical strategy for gastrointestinal tract malignancy is en bloc resection, which consists of not only resection of the involved organs but also simultaneous resection of the surrounding or adjacent mesenteries that contain lymph vessels and nodes. After resection of the diseased organs, the defect of the gastrointestinal conduit is replaced with organs located downstream, such as the stomach and jejunum. However, esophageal and gastric reconstruction using these natural substitutes is associated with a diminished quality of life due to the loss of the reserve function, damage to the antireflux barrier, and dumping syndrome. Thus, replacement of the deficit after resection with the patient's own regenerated tissue to compensate for the lost function and tissue using regenerative medicine will be an ideal treatment. Many researchers have been trying to construct artificial organs through tissue engineering techniques; however, none have yet succeeded in growing a whole organ because of the complicated functions these organs perform, such as the processing and absorption of nutrients. While exciting results have been reported with regard to tissue engineering techniques concerning the upper gastrointestinal tract, such as the esophagus and stomach, most of these achievements have been observed in animal models, and few successful approaches in the clinical setting have been reported for the replacement of mucosal defects. We review the recent progress in regenerative medicine in relation to the upper gastrointestinal tract, such as the esophagus and stomach. We also focus on the functional capacity of regenerated tissue and its role as a culture system to recapitulate the mechanisms underlying infectious disease. With the emergence of technology such as the fabrication of decellularized constructs, organoids and cell sheet medicine, collaboration between gastrointestinal surgery and regenerative medicine is expected to help establish novel therapeutic modalities in the future.