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Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes
Katsuhisa Matsuura1, Toshio Nagai, Nobuhiro Nishigaki
1Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Insights
Adult mouse hearts contain Sca-1-positive (Sca-1+) cells with stem cell properties. These cardiac stem cells can differentiate into beating cardiomyocytes and other cell types, suggesting potential for heart regeneration.
Area of Science:
- Cardiology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Somatic stem cells are found in various adult organs, but their presence and function in the heart remain under-investigated.
- Identifying cardiac stem cells is crucial for understanding heart repair mechanisms.
Purpose of the Study:
- To investigate the stem cell potential of Sca-1-positive (Sca-1+) cells isolated from adult murine hearts.
- To characterize the differentiation capacity of these cardiac Sca-1+ cells.
Main Methods:
- Isolation of Sca-1+ cells from adult murine hearts using magnetic cell sorting.
- Culture of isolated cells and induction of differentiation using oxytocin and isoproterenol.
- Assessment of cardiac gene expression, protein structure, spontaneous beating, intracellular calcium transients, and differentiation into osteogenic and adipogenic lineages.
Main Results:
- A fraction of Sca-1+ cells adhered to culture dishes and exhibited slow proliferation.
- Oxytocin treatment induced expression of cardiac transcription factors and contractile proteins, leading to sarcomeric structure and spontaneous beating.
- Isoproterenol enhanced beating rate, correlated with intracellular Ca(2+) transients.
- Cardiac Sca-1+ cells expressed oxytocin receptor mRNA, with upregulated expression after oxytocin treatment.
- Some Sca-1+ cells differentiated into osteogenic and adipogenic lineages, indicated by alkaline phosphatase expression and Oil-Red O staining, respectively.
Conclusions:
- Adult murine heart Sca-1+ cells possess stem cell-like characteristics.
- These cells demonstrate potential for differentiation into cardiomyocytes and other cell types.
- Cardiac Sca-1+ cells may play a role in the regeneration of injured heart tissue.
Abstract:
Although somatic stem cells have been reported to exist in various adult organs, there have been few reports concerning stem cells in the heart. We here demonstrate that Sca-1-positive (Sca-1+) cells in adult hearts have some of the features of stem cells. Sca-1+ cells were isolated from adult murine hearts by a magnetic cell sorting system and cultured on gelatin-coated dishes. A fraction of Sca-1+ cells stuck to the culture dish and proliferated slowly. When treated with oxytocin, Sca-1+ cells expressed genes of cardiac transcription factors and contractile proteins and showed sarcomeric structure and spontaneous beating. Isoproterenol treatment increased the beating rate, which was accompanied by the intracellular Ca(2+) transients. The cardiac Sca-1+ cells expressed oxytocin receptor mRNA, and the expression was up-regulated after oxytocin treatment. Some of the Sca-1+ cells expressed alkaline phosphatase after osteogenic induction and were stained with Oil-Red O after adipogenic induction. These results suggest that Sca-1+ cells in the adult murine heart have potential as stem cells and may contribute to the regeneration of injured hearts.
