Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in inflammatory bowel disease.
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.
Lanzoni
Giacomo
G
Department of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy. giacomo.lanzoni@unibo.it
Alviano
Francesco
F
Marchionni
Cosetta
C
Bonsi
Laura
L
Costa
Roberta
R
Foroni
Laura
L
Roda
Giulia
G
Belluzzi
Andrea
A
Caponi
Alessandra
A
Ricci
Francesca
F
Luigi Tazzari
Pier
P
Pagliaro
Pasqualepaolo
P
Rizzo
Roberta
R
Lanza
Francesco
F
Roberto Baricordi
Olavio
O
Pasquinelli
Gianandrea
G
Roda
Enrico
E
Paolo Bagnara
Gian
G
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
D015415:Biomarkers; D010835:Phytohemagglutinins