Tissue-engineered small intestine: ontogeny of the immune system

Using tissue-engineering techniques, we have developed a that regenerates structural and transporter properties of native jejunum. The purpose of this study was to characterize the mucosal immune system of the engineered neointestine. We hypothesized that the neointestinal mucosa is capable of developing a mature immunocyte population and that exposure to luminal stimuli is critical to this development.

Neointestinal cysts were engineered by implanting polymer-organoid constructs into syngeneic adult recipients. Neointestine (cysts left nonanastomosed [NA] and cysts anastomosed to native bowel [AN]) and native jejunum were harvested serially (3-56 weeks postoperatively). Immune cell subsets were characterized by the immunohistochemical detection of cell-specific antigens (T cells [CD3], B cells [CD32], NK cells [CD56], and macrophages [CD68]) combined with computer-based morphometry.

Intraepithelial and lamina propria immunocyte population densities and subset distributions were identical in AN cysts harvested 20 weeks postoperatively and in native jejunum. Mucosal immunocyte population densities were lower in AN cysts harvested 10 weeks postoperatively and only rudimentary in NA cysts, even those harvested 20 weeks postoperatively.

These results suggest that tissue-engineered intestine has the capacity to develop a mucosal immune system with an immunocyte population similar to that of native small intestine. The development of this immune system is a function of both exposure to luminal stimuli and the duration of this exposure. Tissue-engineered intestine offers promise as a new therapeutic approach for patients who have intestinal insufficiency.