title: Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in inflammatory bowel disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy. giacomo.lanzoni@unibo.it
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lanzoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Alviano
authors.forename: Cosetta
authors.initials: C
authors.lastname: Marchionni
authors.forename: Laura
authors.initials: L
authors.lastname: Bonsi
authors.forename: Roberta
authors.initials: R
authors.lastname: Costa
authors.forename: Laura
authors.initials: L
authors.lastname: Foroni
authors.forename: Giulia
authors.initials: G
authors.lastname: Roda
authors.forename: Andrea
authors.initials: A
authors.lastname: Belluzzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Caponi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Pier
authors.initials: P
authors.lastname: Luigi Tazzari
authors.forename: Pasqualepaolo
authors.initials: P
authors.lastname: Pagliaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Lanza
authors.forename: Olavio
authors.initials: O
authors.lastname: Roberto Baricordi
authors.forename: Gianandrea
authors.initials: G
authors.lastname: Pasquinelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Roda
authors.forename: Gian
authors.initials: G
authors.lastname: Paolo Bagnara
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D033581:Stem Cell Transplantation
chemical_list: D015415:Biomarkers; D010835:Phytohemagglutinins