title: Identity and ranking of colonic mesenchymal stromal cells.
abstract: Although ongoing clinical trials utilize systemic administration of bone-marrow mesenchymal stromal cells (BM-MSCs) in Crohn's disease (CD), nothing is known about the presence and the function of mesenchymal stromal cells (MSCs) in the normal human bowel. MSCs are bone marrow (BM) multipotent cells supporting hematopoiesis with the potential to differentiate into multiple skeletal phenotypes. A recently identified new marker, CD146, allowing to prospectively isolate MSCs from BM, renders also possible their identification in different tissues. In order to elucidate the presence and functional role of MSCs in human bowel we analyzed normal adult colon sections and isolated MSCs from them. In colon (C) sections, resident MSCs form a net enveloping crypts in lamina propria, coinciding with structural myofibroblasts or interstitial stromal cells. Nine sub-clonal CD146(+) MSC lines were derived and characterized from colon biopsies, in addition to MSC lines from five other human tissues. In spite of a phenotype qualitative identity between the BM- and C-MSC populations, they were discriminated and categorized. Similarities between C-MSC and BM-MSCs are represented by: Osteogenic differentiation, hematopoietic supporting activity, immune-modulation, and surface-antigen qualitative expression. The differences between these populations are: C-MSCs mean intensity expression is lower for CD13, CD29, and CD49c surface-antigens, proliferative rate faster, life-span shorter, chondrogenic differentiation rare, and adipogenic differentiation completely blocked. Briefly, BM-MSCs, deserve the rank of progenitors, whereas C-MSCs belong to the restricted precursor hierarchy. The presence and functional role of MSCs in human colon provide a rationale for BM-MSC replacement therapy in CD, where resident bowel MSCs might be exhausted or diverted from their physiological functions.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Signore
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cerio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Boe
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pagliuca
authors.forename: Valentina
authors.initials: V
authors.lastname: Zaottini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Schiavoni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fedele
authors.forename: Stefano
authors.initials: S
authors.lastname: Petti
authors.forename: Simone
authors.initials: S
authors.lastname: Navarra
authors.forename: Clara Maria
authors.initials: CM
authors.lastname: Ausiello
authors.forename: Elvira
authors.initials: E
authors.lastname: Pelosi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fatica
authors.forename: Antonio
authors.initials: A
authors.lastname: Sorrentino
authors.forename: Mauro
authors.initials: M
authors.lastname: Valtieri
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D001854:Bone Marrow Cells / Q000166:cytology; D051929:CD146 Antigen / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D020219:Chondrogenesis / Q000502:physiology; D003106:Colon / Q000166:cytology / Q000254:growth & development*; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D058628:Myofibroblasts; D010012:Osteogenesis / Q000502:physiology
chemical_list: D015415:Biomarkers; D051929:CD146 Antigen; C497902:MCAM protein, human