Cardiogel as an Instructive Microenvironment for in vitro Differentiation of Bone Marrow- Derived Mesenchymal Stem Cells into Cardiomyocytes

Document Type: Original Article

Authors

1 Assistant Professor, Immunogenetic Research Center & Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2 Assistant Professor, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Assistant Professor, Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran & Institute of Neuropharmacology, Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

4 Ph.D. Student of Anatomy, Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Associate Professor, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

6 Assistant Professor, Department of Basic Sciences, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

7 Assistant Professor of Anatomy, Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Stem cell therapy has been developed as an effective treatment method for the heart failure. Also, extracellular matrix has shown the positive effects in stem cell differentiation and myocardial tissue organization. Cardiogel is a native cardiac extracellular matrix (ECM) derived from cardiac fibroblasts. In the present study the role of cardiogel is examined for its cardiomyogenic potential on mouse bone marrow- derived mesenchymal stem cells (BM-MSCs).
Method: The BM-MSCs were isolated from six-week-old mice. Cardiac fibroblasts were collected from neonatal heart mice and the cells were seeded on 0.2% gelatin pre-coated plates for up to 21 days. Then, the decellularization was performed via enzymatic digestion. For cardiomyocyte differentiation, the BM-MSCs were plated on matrix-coated plates (Cardiogel, CCP), Matrigel-coated plates (MCP) and gelatin-coated plates (GCP) as a control group at a density of 1 × 104 cells per cm2 in CM containing 3 mM 5-azacytidine.
Results: The results proved that cardiogel is capable to promote the cardiomyogenic differentiation of BM-MSCs. Cardiogel had a great influence on cellular adhesion, gene expression and cardiomyocyte differentiation compared to MCP and GCP. Gene expression analysis showed that cardiac specific markers were expressed in BM-MSCs has grown in CCP that represented the cardiac-specific differentiation.
Conclusion: Our results suggest that cardiogel is an effective ECM that can improve the cardiomyogenic differentiation of BM-MSCs, and it can be used as a possible therapeutic approach in cardiac tissue regeneration.

Keywords


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