In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

2012 May 31 | Li Qian, Yu Huang, C. Ian Spencer, Amy Foley, Vasanth Vedantham, Lei Liu, Simon J. Conway, Ji-dong Fu, Deepak Srivastava
In a study published in Nature (2012), researchers demonstrate that cardiac fibroblasts in the mouse heart can be reprogrammed into cardiomyocyte-like cells in vivo using the transcription factors Gata4, Mef2c, and Tbx5 (GMT). This reprogramming was achieved through local delivery of GMT after coronary ligation, leading to the formation of bi-nucleate, sarcomere-containing cells with cardiomyocyte-like gene expression. These cells exhibited ventricular-like action potentials, electrical coupling, and improved cardiac function. When combined with Thymosin β4, a pro-angiogenic and fibroblast-activating peptide, scar area and cardiac function were further improved. The findings suggest that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment, offering potential for regenerative medicine. The study also shows that these reprogrammed cells can integrate with existing cardiomyocytes, enhancing cardiac function and reducing infarct size. The research highlights the potential of cellular reprogramming in treating heart failure and improving cardiac function. The study involved a range of techniques, including genetic lineage tracing, immunohistochemistry, and electrophysiology, to assess the reprogramming process and its effects on cardiac function. The results indicate that reprogramming cardiac fibroblasts into cardiomyocyte-like cells could be a promising approach for regenerative therapy in heart disease.In a study published in Nature (2012), researchers demonstrate that cardiac fibroblasts in the mouse heart can be reprogrammed into cardiomyocyte-like cells in vivo using the transcription factors Gata4, Mef2c, and Tbx5 (GMT). This reprogramming was achieved through local delivery of GMT after coronary ligation, leading to the formation of bi-nucleate, sarcomere-containing cells with cardiomyocyte-like gene expression. These cells exhibited ventricular-like action potentials, electrical coupling, and improved cardiac function. When combined with Thymosin β4, a pro-angiogenic and fibroblast-activating peptide, scar area and cardiac function were further improved. The findings suggest that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment, offering potential for regenerative medicine. The study also shows that these reprogrammed cells can integrate with existing cardiomyocytes, enhancing cardiac function and reducing infarct size. The research highlights the potential of cellular reprogramming in treating heart failure and improving cardiac function. The study involved a range of techniques, including genetic lineage tracing, immunohistochemistry, and electrophysiology, to assess the reprogramming process and its effects on cardiac function. The results indicate that reprogramming cardiac fibroblasts into cardiomyocyte-like cells could be a promising approach for regenerative therapy in heart disease.
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