Abstract

The heart was initially believed to be a terminally differentiated organ; once the cardiomyocytes died, no recovery could be made to replace the dead cells. However, around a decade ago, the concept of cardiac stem cells (CSCs) in adult hearts was proposed. CSCs differentiate into cardiomyocytes, keeping the heart functioning. Studies have proved the existence of stem cells in the heart. These somatic stem cells have been studied for use in cardiac regeneration. Moreover, recently, induced pluripotent stem cells (iPSCs) were invented, and methodologies have now been developed to induce stable cardiomyocyte differentiation and purification of mature cardiomyocytes. A reprogramming method has also been applied to direct reprogramming using cardiac fibroblasts into cardiomyocytes. Here, we address cardiomyocyte differentiation of CSCs and iPSCs. Furthermore, we describe the potential of CSCs in regenerative biology and regenerative medicine.

Highlights

  • Heart failure, which is one of the major causes of death worldwide [1,2], occurs mainly due to the dysfunction of cardiomyocytes

  • We address the potential of induced pluripotent stem cell-derived cardiomyocytes and direct reprogramming of somatic cells into cardiomyocytes, a strategy that has been rapidly and efficiently developed in recent years

  • The stem cells isolated as c-Kit positive cells from the bone marrow (BM) were shown to differentiate into cardiomyocytes in an ischemic heart to regenerate a damaged heart [29]

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Summary

Introduction

Heart failure, which is one of the major causes of death worldwide [1,2], occurs mainly due to the dysfunction of cardiomyocytes. If there are no new cells to replace the damaged cells, transplantation is the only treatment to cure heart failure. The major cell surface markers used for isolation were c-Kit and multi-drug resistance protein (MDR)-1 in various vertebrates [5,9±11], as well as stem cell antigen (Sca)-1 [6]. CSCs were recently used in clinical trials ([26] and [27], respectively). Transplantation of these stem cells has been successful for improving myocardial infarct (MI)-induced damage in animal models. The major effect of BMCs is not due to stem-cell differentiation into cardiomyocytes as previously expected, but rather in progressing angiogenesis.

Stem Cells Used for Cardiomyocyte Regeneration
Adult CSCs
Cardiosphere-Forming Cells
Other Stem Cells Relating to the Heart
Left-Atrium-Derived c-Kit Positive Cells
Similarity of LA-PCs to Other Stem Cells
Microarray Analysis for Identification
Noggin and Cardiac Myocytes
Direct Reprogramming to Induce Cardiomyocyte Differentiation
Regenerative Medicine Using Stem Cells
Findings
Conclusion
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