Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment
Human resident cardiac progenitor cells (CPCs) isolated as cardiosphere-derived cells (CDCs) are under clinical evaluation as a therapeutic product for cardiac regenerative medicine. Unfortunately, limited engraftment and differentiation potential of transplanted cells significantly hamper therapeut...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/7396462 |
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| author | Francesca Pagano Francesco Angelini Clotilde Castaldo Vittorio Picchio Elisa Messina Sebastiano Sciarretta Ciro Maiello Giuseppe Biondi-Zoccai Giacomo Frati Franca di Meglio Daria Nurzynska Isotta Chimenti |
| author_facet | Francesca Pagano Francesco Angelini Clotilde Castaldo Vittorio Picchio Elisa Messina Sebastiano Sciarretta Ciro Maiello Giuseppe Biondi-Zoccai Giacomo Frati Franca di Meglio Daria Nurzynska Isotta Chimenti |
| author_sort | Francesca Pagano |
| collection | DOAJ |
| description | Human resident cardiac progenitor cells (CPCs) isolated as cardiosphere-derived cells (CDCs) are under clinical evaluation as a therapeutic product for cardiac regenerative medicine. Unfortunately, limited engraftment and differentiation potential of transplanted cells significantly hamper therapeutic success. Moreover, maladaptive remodelling of the extracellular matrix (ECM) during heart failure progression provides impaired biological and mechanical signals to cardiac cells, including CPCs. In this study, we aimed at investigating the differential effect on the phenotype of human CDCs of cardiac fibroblast-derived ECM substrates from healthy or diseased hearts, named, respectively, normal or pathological cardiogel (CG-N/P). After 7 days of culture, results show increased levels of cardiogenic gene expression (NKX2.5, CX43) on both decellularized cardiogels compared to control, while the proportion and staining patterns of GATA4, OCT4, NKX2.5, ACTA1, VIM, and CD90-positive CPCs were not affected, as assessed by immunofluorescence microscopy and flow cytometry analyses. Nonetheless, CDCs cultured on CG-N secreted significantly higher levels of osteopontin, FGF6, FGF7, NT-3, IGFBP4, and TIMP-2 compared to those cultured on CG-P, suggesting overall a reduced trophic and antiremodelling paracrine profile of CDCs when in contact with ECM from pathological cardiac fibroblasts. These results provide novel insights into the bidirectional interplay between cardiac ECM and CPCs, potentially affecting CPC biology and regenerative potential. |
| format | Article |
| id | doaj-art-3992e8fb78e0472ea2edb0f2bebbfd1d |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-3992e8fb78e0472ea2edb0f2bebbfd1d2025-08-20T03:55:12ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/73964627396462Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and CommitmentFrancesca Pagano0Francesco Angelini1Clotilde Castaldo2Vittorio Picchio3Elisa Messina4Sebastiano Sciarretta5Ciro Maiello6Giuseppe Biondi-Zoccai7Giacomo Frati8Franca di Meglio9Daria Nurzynska10Isotta Chimenti11Department of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyDepartment of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyDepartment of Public Health, University of Naples “Federico II”, Naples, ItalyDepartment of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyDepartment of Pediatrics and Childhood Neuropsychiatry, “Umberto I” Hospital, “La Sapienza” University of Rome, Rome, ItalyDepartment of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyDepartment of Cardiothoracic Sciences, Monaldi Hospital, Second University of Naples, Caserta, ItalyDepartment of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyDepartment of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyDepartment of Public Health, University of Naples “Federico II”, Naples, ItalyDepartment of Public Health, University of Naples “Federico II”, Naples, ItalyDepartment of Medical Surgical Sciences and Biotechnologies, “La Sapienza” University of Rome, Rome, ItalyHuman resident cardiac progenitor cells (CPCs) isolated as cardiosphere-derived cells (CDCs) are under clinical evaluation as a therapeutic product for cardiac regenerative medicine. Unfortunately, limited engraftment and differentiation potential of transplanted cells significantly hamper therapeutic success. Moreover, maladaptive remodelling of the extracellular matrix (ECM) during heart failure progression provides impaired biological and mechanical signals to cardiac cells, including CPCs. In this study, we aimed at investigating the differential effect on the phenotype of human CDCs of cardiac fibroblast-derived ECM substrates from healthy or diseased hearts, named, respectively, normal or pathological cardiogel (CG-N/P). After 7 days of culture, results show increased levels of cardiogenic gene expression (NKX2.5, CX43) on both decellularized cardiogels compared to control, while the proportion and staining patterns of GATA4, OCT4, NKX2.5, ACTA1, VIM, and CD90-positive CPCs were not affected, as assessed by immunofluorescence microscopy and flow cytometry analyses. Nonetheless, CDCs cultured on CG-N secreted significantly higher levels of osteopontin, FGF6, FGF7, NT-3, IGFBP4, and TIMP-2 compared to those cultured on CG-P, suggesting overall a reduced trophic and antiremodelling paracrine profile of CDCs when in contact with ECM from pathological cardiac fibroblasts. These results provide novel insights into the bidirectional interplay between cardiac ECM and CPCs, potentially affecting CPC biology and regenerative potential.http://dx.doi.org/10.1155/2017/7396462 |
| spellingShingle | Francesca Pagano Francesco Angelini Clotilde Castaldo Vittorio Picchio Elisa Messina Sebastiano Sciarretta Ciro Maiello Giuseppe Biondi-Zoccai Giacomo Frati Franca di Meglio Daria Nurzynska Isotta Chimenti Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment Stem Cells International |
| title | Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment |
| title_full | Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment |
| title_fullStr | Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment |
| title_full_unstemmed | Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment |
| title_short | Normal versus Pathological Cardiac Fibroblast-Derived Extracellular Matrix Differentially Modulates Cardiosphere-Derived Cell Paracrine Properties and Commitment |
| title_sort | normal versus pathological cardiac fibroblast derived extracellular matrix differentially modulates cardiosphere derived cell paracrine properties and commitment |
| url | http://dx.doi.org/10.1155/2017/7396462 |
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