• In vivo Cardiac Reprogramming as a Strategy for the Treatment of Heart Disease
  • Sanaz Panahi Alanagh,1 Fatemeh Amin,2 Mahsa Ghiasvand,3 Mahmood Talkhabi,4,*
    1. Department of Animal Biology and Biotechnology, Faculty of Life Sciences and Biotechnology, University of Shahid Beheshti, Tehran, Iran
    2. Department of Animal Biology and Biotechnology, Faculty of Life Sciences and Biotechnology, University of Shahid Beheshti, Tehran, Iran
    3. Department of Animal Biology and Biotechnology, Faculty of Life Sciences and Biotechnology, University of Shahid Beheshti, Tehran, Iran
    4. Department of Animal Biology and Biotechnology, Faculty of Life Sciences and Biotechnology, University of Shahid Beheshti, Tehran, Iran


  • Introduction: Cardiovascular diseases (CVD), which account for approximately 33% of all deaths worldwide, are the leading cause of morbidity and mortality for people of most ethnicities. These conditions include heart disease, stroke, heart failure (HF), and myocardial infarction (MI). The adult human heart's inadequate potential for cardiac regeneration is the key factor that places CVD at the top of the mortality list. In place of other treatment modalities like heart transplantation, cardiac regenerative medicine can restore the structure and function of the heart.
  • Methods: One of the potential approaches in heart regenerative medicine is the use of de novo generated cardiomyocytes (CMs) in cardiac cell-based treatment. To do this, many types of multipotent and pluripotent stem cells (PSCs) have been investigated to create cardiac lineage cells, such as cardiac progenitor cells (CPCs) and CMs, which are needed in cardiac regenerative medicine. Direct reprogramming, also known as a direct conversion, is a recently developed technique that directly transforms somatic cells into cardiac cells in vitro and in vivo. Through the activation of cardiogenesis-related or pluripotency-inducing factors in non-cardiac cells, this cellular alchemy provides a quick and secure method for producing autologous cardiac cells. The definition of direct conversion is the creation of either a functional mature such as CM. That develops a second fully developed somatic cell without passing through pluripotency The ethical problems associated with ESCs are solved by this technique since the starting cells are patient-derived somatic cells (for example, skin-derived fibroblasts). This method has received attention for the past twelve years as a way to produce de novo cardiac lineage cells (CPCs/CMs). In general, there are two methods for direct cardiac conversion: short-term overexpression of pluripotency-inducing factors (such as Oct4, Sox2, Klf4, and C-myc [OSKM]) in somatic starting cells, which results in the formation of unstable intermediates that can be reprogrammed; and long-term overexpression of cardiogenesis-specific factors such as transcription factors and miRNA in starting somatic cells may result in the formation of unstable intermediates that can be differentiated or regulated to have a cardiac destiny using signals that induce cardiogenesis.
  • Results: Importantly, direct cardiac conversion based on pluripotency factors, also known as partial reprogramming, is quicker and more effective in producing CM in vitro. Also using transgene-free, chemical-based methods, it is now possible to directly convert somatic mice and human cells into cardiac lineage cells.
  • Conclusion: Although it is difficult to convert cardiac fibroblasts into cardiac cells in vivo via heart-specific partial reprogramming. Furthermore, assuming the safety concerns are resolved, cardiac cells created utilizing a partial reprogramming approach might be a helpful platform for disease modeling, drug screening, and cardiac cell-based treatment. In this study, we have evaluated all the reports that have been worked on in vivo cardiac reprogramming.
  • Keywords: Cardiac reprogramming, partial reprogramming, pluripotency-inducing factors, cardiogenesis-specific.