Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells
The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the ca...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/4969430 |
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| author | Giacomo Palazzolo Mattia Quattrocelli Jaan Toelen Roberto Dominici Luigi Anastasia Guido Tettamenti Inès Barthelemy Stephane Blot Rik Gijsbers Marco Cassano Maurilio Sampaolesi |
| author_facet | Giacomo Palazzolo Mattia Quattrocelli Jaan Toelen Roberto Dominici Luigi Anastasia Guido Tettamenti Inès Barthelemy Stephane Blot Rik Gijsbers Marco Cassano Maurilio Sampaolesi |
| author_sort | Giacomo Palazzolo |
| collection | DOAJ |
| description | The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs). We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C), known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis. |
| format | Article |
| id | doaj-art-7718401dbd8c4e8892cd230b5ec5be4a |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-7718401dbd8c4e8892cd230b5ec5be4a2025-08-20T03:35:45ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/49694304969430Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like CellsGiacomo Palazzolo0Mattia Quattrocelli1Jaan Toelen2Roberto Dominici3Luigi Anastasia4Guido Tettamenti5Inès Barthelemy6Stephane Blot7Rik Gijsbers8Marco Cassano9Maurilio Sampaolesi10Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, Herestraat 49 O&N4 Bus 814, 3000 Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, Herestraat 49 O&N4 Bus 814, 3000 Leuven, BelgiumOrgan Systems Development and Regeneration Unit, Department of Development and Regeneration, KU Leuven, Herestraat 49 O&N4 Bus 814, 3000 Leuven, BelgiumLaboratory of Clinical Chemistry, Public Health Corporation of Legnano, Magenta Hospital, 20013 Magenta, ItalyLaboratory of Stem Cells for Tissue Engineering, IRCCS, San Donato Hospital, San Donato, Milan, ItalyLaboratory of Stem Cells for Tissue Engineering, IRCCS, San Donato Hospital, San Donato, Milan, ItalyLaboratoire de Neurobiologie, Ecole Nationale Vétérinaire d’Alfort, 94704 Maisons-Alfort, FranceLaboratoire de Neurobiologie, Ecole Nationale Vétérinaire d’Alfort, 94704 Maisons-Alfort, FranceLaboratory of Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences and Leuven Viral Vector Core, KU Leuven, Leuven, BelgiumSchool of Life Sciences, EPFL, 1015 Lausanne, SwitzerlandTranslational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, Herestraat 49 O&N4 Bus 814, 3000 Leuven, BelgiumThe Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs). We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C), known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis.http://dx.doi.org/10.1155/2016/4969430 |
| spellingShingle | Giacomo Palazzolo Mattia Quattrocelli Jaan Toelen Roberto Dominici Luigi Anastasia Guido Tettamenti Inès Barthelemy Stephane Blot Rik Gijsbers Marco Cassano Maurilio Sampaolesi Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells Stem Cells International |
| title | Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells |
| title_full | Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells |
| title_fullStr | Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells |
| title_full_unstemmed | Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells |
| title_short | Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells |
| title_sort | cardiac niche influences the direct reprogramming of canine fibroblasts into cardiomyocyte like cells |
| url | http://dx.doi.org/10.1155/2016/4969430 |
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