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      Cardiomyocyte Regeneration

      review-article
      Author(s): * ,
      Publication date (Electronic):
      Journal: Cells
      Publisher: MDPI
      Keywords: heart, cardiomyocyte, stem cell, TGF-β, differentiation, regenerative medicine, c-Kit, myocardial, infarct, cardiac stem cell

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          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.

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          Reprogramming of human somatic cells to pluripotency with defined factors.

          In-Hyun Park, Rui Zhao, Jason A. West … (2008)
          Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.
          Article 0 comments Cited 662 times – based on 0 reviews     Review now
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            In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

            Li Qian, Yu Huang, C Spencer … (2012)
            SUMMARY The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here, we use genetic lineage-tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became bi-nucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast activating peptide, Thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes.
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              Heart repair by reprogramming non-myocytes with cardiac transcription factors

              Kunhua Song, Young-Jae Nam, Xiang Luo … (2012)
              The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, Hand2, MEF2C and Tbx5 can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodeling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cells
                Journal ID (iso-abbrev): Cells
                Journal ID (publisher-id): cells
                Title: Cells
                Publisher: MDPI
                ISSN (Electronic): 2073-4409
                Publication date (Electronic): 15 January 2013
                Publication date Collection: March 2013
                Volume: 2
                Issue: 1
                Pages: 67-82
                Affiliations
                Department of Pediatric Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan; E-Mail: nakanishi@ 123456imcir.twmu.ac.jp
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: nanako.res@ 123456gmail.com .
                Article
                Publisher ID: cells-02-00067
                DOI: 10.3390/cells2010067
                PMC ID: 3972659
                SO-VID: fe1cd3f2-afe1-4b30-9e2f-d329b10018ff
                Copyright © © 2013 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 03 September 2012
                Date revision received : 25 December 2012
                Date accepted : 05 January 2013
                Categories
                Subject: Review

                Keywords: heart,cardiomyocyte,stem cell,tgf-β,differentiation,regenerative medicine,c-kit,myocardial,infarct,cardiac stem cell
                Data availability:
                Keywords: heart, cardiomyocyte, stem cell, tgf-β, differentiation, regenerative medicine, c-kit, myocardial, infarct, cardiac stem cell

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