Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation
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 ApcMin/+ mice were transplanted with bone ma...
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| Format: | Article |
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Wiley
2015-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2015/354193 |
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| author | Michele Barone Maria Principia Scavo Raffaele Licinio Michele Piombino Nicola De Tullio Rosanna Mallamaci Alfredo Di Leo |
| author_facet | Michele Barone Maria Principia Scavo Raffaele Licinio Michele Piombino Nicola De Tullio Rosanna Mallamaci Alfredo Di Leo |
| author_sort | Michele Barone |
| collection | DOAJ |
| description | 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 ApcMin/+ mice were transplanted with bone marrow (BM) cells obtained from either male age-matched ApcMin/+ (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 ApcMin/+ 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. |
| format | Article |
| id | doaj-art-1fe7e11955a6416891db891248e07280 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-1fe7e11955a6416891db891248e072802025-02-03T01:21:17ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/354193354193Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ MutationMichele Barone0Maria Principia Scavo1Raffaele Licinio2Michele Piombino3Nicola De Tullio4Rosanna Mallamaci5Alfredo Di Leo6Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, ItalyGastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, ItalyGastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, ItalyRadiotherapy Unit, Diagnostic Imaging Department, Polyclinic Hospital, Piazza G. Cesare 11, 70124 Bari, ItalyGastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, ItalyDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70124 Bari, ItalyGastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Piazza G. Cesare 11, 70124 Bari, ItalyWe 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 ApcMin/+ mice were transplanted with bone marrow (BM) cells obtained from either male age-matched ApcMin/+ (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 ApcMin/+ 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.http://dx.doi.org/10.1155/2015/354193 |
| spellingShingle | Michele Barone Maria Principia Scavo Raffaele Licinio Michele Piombino Nicola De Tullio Rosanna Mallamaci Alfredo Di Leo Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation Stem Cells International |
| title | Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation |
| title_full | Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation |
| title_fullStr | Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation |
| title_full_unstemmed | Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation |
| title_short | Role of Bone Marrow-Derived Stem Cells in Polyps Development in Mice with ApcMin/+ Mutation |
| title_sort | role of bone marrow derived stem cells in polyps development in mice with apcmin mutation |
| url | http://dx.doi.org/10.1155/2015/354193 |
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