Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in inflammatory bowel disease

Background: Mesenchymal Stromal Cells (MSCs) are multipotent progenitor cells able to perform trophic and immunomodulatory functions, and are currently under evaluation in phase III clinical trials for Inflammatory Bowel Disease manifestations. Populations sharing MSC characteristics have been found in several tissues: dissimilarities have been shown in differentiation and trophic abilities. Little is known about the presence and role of cells with stem characteristics in the intestinal stromal compartment. Isolation of such populations may lead to new insights into the biological roles and kinetics of intestinal stromal tissues, and may open a new scenario for regenerative medicine in this field. Methods: Intestinal specimens were collected, mucosa and submucosa were mechanically separated and enzymatically digested. Mesenchymal stromal populations were isolated, expanded and characterized under conditions commonly used for MSCs. The differentiation potential, trophic effect and immunomodulatory ability were investigated. Results: We successfully isolated and extensively expanded populations showing the typical MSC profile: CD29+, CD44+, CD73+, CD105+, CD166+ and CD14-, CD34-, CD45-. Intestinal Mucosal-Mesenchymal Stromal Cells (IM-MSCs) were also CD117+ while SubMucosal cultures (ISM-MSCs) showed CD34+ subsets. The cells differentiated toward osteogenic, adipogenic and angiogenic commitments. Intestinal-derived MSCs were able to induce differentiation and organization of intestinal epithelial cells (Caco-2) in collagen cultures. Immunomodulatory activity was evidenced in co-cultures with phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusions: Multipotent MSCs can be isolated from intestinal mucosal and submucosal tissues. IM-MSCs and ISM-MSCs are able to perform trophic and immunomodulatory functions. These findings could open a pathway for novel approaches to IBD treatment.