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

• Published in: Cytotherapy (Oxford, England) England), 2009, Vol.11 (8), p.1020-1031
• Main Authors: Lanzoni, Giacomo, Alviano, Francesco, Marchionni, Cosetta, Bonsi, Laura, Costa, Roberta, Foroni, Laura, Roda, Giulia, Belluzzi, Andrea, Caponi, Alessandra, Ricci, Francesca, Luigi Tazzari, Pier, Pagliaro, Pasqualepaolo, Rizzo, Roberta, Lanza, Francesco, Roberto Baricordi, Olavio, Pasquinelli, Gianandrea, Roda, Enrico, Paolo Bagnara, Gian
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Biomarkers - metabolism; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Line; Cell Lineage - drug effects; Cell Proliferation - drug effects; Cell Separation - methods; cell therapy; Epithelial Cells - cytology; Epithelial Cells - drug effects; Humans; immunomodulation; Immunomodulation - drug effects; inflammatory bowel disease; Inflammatory Bowel Diseases - therapy; Intestinal Mucosa - cytology; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; intestinal stem cell; Intestines - cytology; mesenchymal stromal cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Neovascularization, Physiologic - drug effects; Osteogenesis - drug effects; Other; Phytohemagglutinins - pharmacology; Stem Cell Transplantation; stem cells; trophic function
• ISSN: 1465-3249; 1477-2566
• DOI: 10.3109/14653240903253840

Background aims Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSC) are currently under evaluation in phase III clinical trials for inflammatory bowel disease and other intestinal disease 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: CD29+ , CD44+ , CD73+ , CD105+ and CD166+ , and CD14− , CD34− and CD45− . Intestinal mucosal (IM) MSC were also CD117+ , while submucosal cultures (ISM MSC) showed CD34+ 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 intestinal disease treatment.