title: Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with Apc(Min/+) Mutation.
abstract: We explored the hypothesis that an altered microenvironment (intestinal adenomatous polyp) could modify the differentiation program of bone marrow-derived stem cells (BMSCs), involving them in colon carcinogenesis. Sublethally irradiated 8-week-old female Apc(Min/+) mice were transplanted with bone marrow (BM) cells obtained from either male age-matched Apc(Min/+) (Apc-Tx-Apc) or wild type (WT) (WT-Tx-Apc) mice. At 4 and 7 weeks after transplantation, BM-derived colonocytes were recognized by colocalization of Y-chromosome and Cdx2 protein (specific colonocyte marker). Polyp number, volume, and grade of dysplasia were not influenced by irradiation/transplantation procedures since they were similar in both untreated female Apc(Min/+) and Apc-Tx-Apc mice. At 4 and 7 weeks after transplantation, a progressive significant reduction of polyp number and volume was observed in WT-Tx-Apc mice. Moreover, the number of WT-Tx-Apc mice with a high-grade dysplastic polyps significantly decreased as compared to Apc-Tx-Apc mice. Finally, at 4 and 7 weeks after transplantation, WT-Tx-Apc mice showed a progressive significant increase of Y+/Cdx2+ cells in "normal" mucosa, whereas, in the adenomatous tissue, Y+/Cdx2+ cells remained substantially unvaried. Our findings demonstrate that WT BMSCs do not participate in polyp development but rather inhibit their growth. The substitution of genotypically altered colonocytes with Y+/Cdx2+ cells probably contributes to this process.
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy ; Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Maria Principia
authors.initials: MP
authors.lastname: Scavo
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Licinio
authors.affiliation: Radiotherapy Unit, Diagnostic Imaging Department, Polyclinic Hospital, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Piombino
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Tullio
authors.affiliation: Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70124 Bari, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mallamaci
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo