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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Cardiac regenerative medicine
Shinsuke Yuasa1, Keiichi Fukuda
1Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan.
Insights
Regenerative cardiac medicine offers hope for severe heart failure. Induced pluripotent stem cells (iPS cells) derived from fibroblasts show promise as an ideal, autologous cell source for repairing heart muscle damage.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Severe heart failure involves irreversible myocardial damage.
- Current therapies are insufficient for myocardial repair.
- Regenerative medicine offers potential solutions for cardiac repair.
Purpose of the Study:
- To explore potential cell sources for regenerative cardiac medicine.
- To evaluate induced pluripotent stem (iPS) cells as a viable option.
- To highlight the integration of diverse scientific fields for cardiac regeneration.
Main Methods:
- Review of experimental and clinical studies on cardiac regenerative medicine.
- Establishment of induced pluripotent stem (iPS) cells from fibroblasts via transcription factor gene transfer (Oct3/4, Sox2, Klf4, c-Myc).
- Assessment of iPS cell differentiation potential and syngeneic properties.
Main Results:
- Embryonic stem (ES) cells are proliferative but not autologous and lack selective cardiomyocyte induction protocols.
- iPS cells can be generated from fibroblasts and differentiate into all three germ layers.
- iPS cells are syngeneic, making them a promising autologous cell source.
Conclusions:
- Induced pluripotent stem cells represent an ideal cell source for regenerative cardiac medicine.
- Further integration of developmental biology, stem cell biology, and tissue engineering is crucial.
- Achieving the full potential of cardiac regenerative medicine requires a multidisciplinary approach.
Abstract:
Severe heart failure is associated with damage to the myocardium that is irreversible with current medical therapies. Recent experimental and clinical studies, however, have opened the possibility of solving many of the associated problems, making this an exciting and tangible goal. There are many potential cell sources for regenerative cardiac medicine, including bone marrow stem cells, endothelial progenitor cells, skeletal myocytes, adult cardiac stem cells, and embryonic stem (ES) cells. Although ES cells are highly proliferative and suitable for mass production, they are not autologous, and an efficient protocol is yet to be established to ensure selective cardiomyocyte induction. Recent studies have successfully established inducible pluripotent stem (iPS) cells from mouse and human fibroblasts by the gene transfer of 4 transcription factors that are strongly expressed in ES cells: Oct3/4, Sox2, Klf4 and c-Myc. iPS cells can differentiate into all 3 germ layer-derived cells and are syngeneic, indicating that they can become an ideal cell source for regenerative medicine. Despite these successes, the accumulating evidence from fields as diverse as developmental biology, stem cell biology and tissue engineering must be integrated to achieve the full potential of cardiac regenerative medicine.
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