Abstract
In developed countries, in which people have nutrient-rich diets, convenient environments, and access to numerous medications, the disease paradigm has changed. Nowadays, heart failure is one of the major causes of death. In spite of this, the therapeutic efficacies of medications are generally unsatisfactory. Although whole heart transplantation is ideal for younger patients with heart failure, many patients are deemed to be unsuitable for this type of surgery due to complications and/or age. The need for therapeutic alternatives to heart transplantation is great. Regenerative therapy is a strong option. For this purpose, several cell sources have been investigated, including intrinsic adult stem or progenitor cells and extrinsic pluripotent stem cells. Most intrinsic stem cells seem to contribute to a regenerative environment via paracrine factors and/or angiogenesis, whereas extrinsic pluripotent stem cells are unlimited sources of cardiomyocytes. In this review, we summarize the various strategies for using regenerative cardiomyocytes including our recent progressions: non-genetic approaches for the purification of cardiomyocytes and efficient transplantation. We expect that use of intrinsic and extrinsic stem cells in combination will enhance therapeutic effectiveness.
Highlights
The heart is designed as a blood pump that works from the earliest organogenetic stage until death
In 1999, we demonstrated that bone marrow mesenchymal stem cells, which we term cardiomyogenesis cells, transdifferentiated into cardiomyocytes after treatment with 5-azacytidine (Makino et al, 1999)
We demonstrated the transplantation of cardiomyogenesis cells into the heart and observed that the integrated cardiomyogenesis cells had features of the adult myocardium (Hattan et al, 2005)
Summary
The heart is designed as a blood pump that works from the earliest organogenetic stage until death. The heart is a complex organ that consists of various types of cells, including cardiomyocytes and non-cardiomyocytes. Non-cardiomyocytes include fibroblasts, endocardial and epicardial cells, vascular endothelial and smooth muscle cells, sympathetic and parasympathetic cells, valvular and chordal cells, and cardiac-resident immune cells. These cell types work co-operatively to create the physiologic heart. There are many candidate cell sources for heart regenerative therapies, such as cardiac-resident, bone marrow, and peripheral blood-derived stem cells. No adult stem cell-based strategy has achieved the production of sufficient numbers of cardiomyocytes to enable functional recovery of the failing heart. It is clear that the primary role of some adult stem cells is the creation of the regenerative environment rather than regeneration of cardiomyocytes. Different strategies are being tested, we believe that these studies will generate safe and effective therapies in the future
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