Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in XXXX .

@entity1944 @entity5750 @entity1195 @entity1759 @entity29 @entity12359 @entity2393 @entity2280 @entity1386
BACKGROUND AIMS: Bone marrow (BM)- and @entity1386 ( @entity1386 )-derived mesenchymal stromal cells (MSC) are currently under evaluation in phase III clinical trials for @entity29 and other @entity1944 manifestations. The therapeutic efficacy of these treatments may derive from a combination of the differentiation, trophic and immunomodulatory abilities of the transplanted cells. We investigated intestinal tissues as sources of MSC: such cells may support tissue-specific functions and hold advantages for engraftment and contribution in the gastrointestinal environment. METHODS: Intestinal specimens were collected, and the mucosa and submucosa mechanically separated and enzymatically digested. Mesenchymal stromal populations were isolated, expanded and characterized under conditions commonly used for MSC. The differentiation potential, trophic effect and immunomodulatory ability were investigated. Results We successfully isolated and extensively expanded populations showing the typical MSC profile: @entity2393 +, @entity1759 +, @entity12359 +, CD105+ and CD166+, and @entity5750 (-), @entity2280 (-) and @entity1195 (-). Intestinal mucosal (IM) MSC were also CD117+, while submucosal cultures (ISM MSC) showed @entity2280 + subsets. The cells differentiated toward osteogenic, adipogenic and angiogenic commitments. Intestinal-derived MSC were able to induce differentiation and organization of intestinal epithelial cells (Caco-2) in three-dimensional collagen cultures. Immunomodulatory activity was evidenced in co-cultures with normal heterologous phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusions Multipotent MSC can be isolated from intestinal mucosal and submucosal tissues. IM MSC and ISM MSC are able to perform trophic and immunomodulatory functions. These findings could open a pathway for novel approaches to @entity1944 treatment.
