Cardiac differentiation is driven by NKX2.5 and GATA4 nuclear translocation in tissue-specific mesenchymal stem cells
| Autor: | Elisa Lledó, José Manuel García-Verdugo, Mauro Llop, Macarmen Bartual, Carolina Gandía, Ana Armiñán, José Anastasio Montero, José Barea, Pilar Sepúlveda, Vicente Mirabet |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Adolescent Cellular differentiation Clinical uses of mesenchymal stem cells Actinin Biology Myocyte Animals Humans Myocytes Cardiac Cells Cultured Stem cell transplantation for articular cartilage repair Cell Nucleus Homeodomain Proteins Myocardium Mesenchymal stem cell Gap Junctions Gene Expression Regulation Developmental Cell Differentiation Mesenchymal Stem Cells Cell Biology Hematology Coculture Techniques Cell biology Culture Media GATA4 Transcription Factor Rats Actin Cytoskeleton Protein Transport Organ Specificity Immunology Antigens Surface Homeobox Protein Nkx-2.5 Stem cell Developmental Biology Adult stem cell Subcellular Fractions Transcription Factors |
| Zdroj: | STEM CELLS AND DEVELOPMENT r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) |
| ISSN: | 1547-3287 |
| Popis: | Myocardial infarction is a major public health problem that causes significant mortality despite recent advances in its prevention and treatment. Therefore, approaches based on adult stem cells represent a promising alternative to conventional therapies for this life-threatening condition. Mesenchymal stem cells (MSCs) are self-renewing pluripotent cells that have been isolated from multiple tissues and differentiate to various cell types. Here we have analyzed the capacity of MSCs from human bone marrow (BMSC), adipose tissue (ATSC), and dental pulp (DPSC) to differentiate to cells with a cardiac phenotype. Differentiation of MSCs was induced by long-term co-culture with neonatal rat cardiomyocytes (CMs). Shortly after the establishment of MSC-CM co-cultures, expression of connexin 43 and the cardiac-specific markers troponin I, beta-myosin heavy chain, atrial natriuretic peptide, and alpha-sarcomeric actinin was detected in BMSCs, ATSCs, and DPSCs. Expression of differentiation markers increased over time in the co-cultures, reaching the highest levels at 4 weeks. Translocation of the transcription factors NKX2.5 and GATA4 to the nucleus was observed in all three cultures of MSCs during the differentiation process; moreover, nuclear localization of NKX2.5 and GATA4 correlated with expression of alpha-sarcomeric actinin. These changes were accompanied by an increase in myofibril organization in the resulting CM-like cells as analyzed by electron microscopy. Thus, our results provide novel information regarding the differentiation of tissue-specific MSCs to cardiomyocytes and support the potential use of MSCs in cell-based cardiac therapies. |
| Databáze: | OpenAIRE |
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