Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle

Matsuura, Kiyotaka; Wada, Hiroshi; Nagai, Toshio; Iijima, Yoshihiro; Minamino, Tohru; Sano, Masanori; Akazawa, Hiroshi; Molkentin, Jeffery D.; Kasanuki, Hiroshi; Komuro, Issei

doi:10.1083/jcb.200312111

Cited by 117 publications

(90 citation statements)

References 53 publications

(75 reference statements)

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“…In short, enhanced green fluorescent protein (EGFP)-labeled BM-MSCs were cocultured with murine cardiomyocytes (see detail in supporting information Material and Methods). In this system, the incidence of cell fusion was around 0.3% [8,9,18] and the evidence of cell fusion-independent cardiomyogenesis was extensively shown in the previous study [5,8,9,11]. In our pilot study, we have confirmed that the incidence of cell fusion was not affected by pioglitazone (0.2%).…”

Section: Cardiomyogenic Induction and Chemical Agentssupporting

confidence: 75%

Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function

et al. 2011

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The efficacy of transplantation of default human marrowderived mesenchymal stem cells (MSCs) was modest. In this study, our challenge was to improve the efficacy of MSC transplantation in vivo by pretreatment of MSCs with pioglitazone. MSCs were cultured with or without medium containing 1 lM of pioglitazone before cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using anti-cardiac troponin-I antibody. For the in vivo experiments, myocardial infarction (MI) at the anterior left ventricle was made in nude rats. Two weeks after MI, MSCs pretreated with pioglitazone (p-BM; n 5 30) or without pioglitazone (BM; n 5 17) were injected, and then survived for 2 weeks. We compared left ventricular function by echocardiogram and immunohistochemistry to observe cardiomyogenic transdifferentiation in vivo. Pretreatment with pioglitazone significantly increased the CTE in vitro (1.9% 6 0.2% n 5 47 vs. 39.5% 6 4.7% n 5 13, p < .05). Transplantation of pioglitazone pretreated MSCs significantly improved change in left ventricular % fractional shortening (BM; 24.8% 6 2.1%, vs. p-BM; 5.2% 6 1.5%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in p-BM in vivo (BM; 0% 6 0% n 5 5, vs. p-BM; 0.077% 6 0.041% n 5 5). Transplantation of pioglitazonepretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source to expect cardiomyogenesis.

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Section: Cardiomyogenic Induction and Chemical Agentssupporting

confidence: 75%

Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function

et al. 2011

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“…Early trials of cardiac repair and regeneration via transplantation of bone marrow-derived stem/progenitor cells have given mixed and modest results (for review see 37 ), indicating that a better understanding of the relevant cell biology is required to provide a consistently effective therapeutic option for stem cell-based regenerative treatments in the heart. The presence of resident eCSCs in the adult heart, including human, has been determined by several groups 2,4,6,[8][9][10]12,14,17,[38][39][40][41][42] . These cells can be isolated and propagated in vitro to produce large numbers of cells without reaching growth arrest or their being a change in cell characteristic.…”

Section: Characterisation Of Ecscsmentioning

confidence: 99%

Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart

et al. 2014

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Article:Smith, AJ orcid.org/0000-0001-7283-5611, Lewis, FC, Aquila, I et al. (6 more authors) (2014) Isolation and characterization of resident endogenous c-Kit cardiac stem cells ⁺ from the adult mouse and rat heart. Nature Protocols, 9 (7). pp. 1662 -1681 . ISSN 1754 -2189 https://doi.org/10.1038/nprot.2014.113 © 2014, Rights Managed by Nature Publishing Group. This is an author produced version of a paper published in Nature Protocols. Uploaded in accordance with the publisher's self-archiving policy.eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. ABSTRACTThis protocol describes the isolation of endogenous c-kit-positive (c-kit pos ), CD45-negative (CD45 neg ) cardiac stem cells (eCSCs), from whole adult mouse and rat hearts. The heart is enzymatically digested via retrograde perfusion of the coronary circulation, resulting in rapid and extensive breakdown of the whole heart. Next the tissue is mechanically dissociated further and cell fractions separated by centrifugation. The c-kit pos CD45 neg eCSC population is isolated by magnetic activated cell sorting technology and purity and cell number assessed by flow cytometry. This process takes approximately 4 hours for mouse eCSCs or 4.5 hours for rat eCSCs. We also describe how to characterise c-kit pos CD45 neg eCSCs. The c-kit pos CD45 neg eCSCs exhibit the defining characteristics of stem cells; being self-renewing, clonogenic and multipotent. This protocol also describes how to differentiate eCSCs into the three main cardiac lineages: functional, beating cardiomyocytes, smooth muscle and endothelial cells. These processes take between 17 and 20 days.

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“…As a result, transplanted stem cells may express the cardiac phenotype and re-enter the cell cycle, which may contribute to myocardial regeneration. This has been proved in an in vitro study in which cardiomyocytes could fuse with endothelial cells, cardiac fibroblasts and bone marrow cells, and the fused cells could re-enter the cell cycle (55). On the other hand, genes of the recipient cell may also be reprogrammed and their expression may be activated or inactivated.…”

Section: Reprinted From Reference 56 With Permissionmentioning

confidence: 91%

A novel approach to studying the transformation of human stem cells into cardiac cells in vivo

Yeh

Zhang

2006

Canadian Journal of Cardiology

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ETH Yeh, S Zhang. A novel approach to studying the transformation of human stem cells into cardiac cells in vivo. Can J Cardiol 2006;22(Suppl B):66B-71B.Stem cell transplantation has been proposed as a novel means of regenerating new myocardium following cardiac damage. Many laboratories have demonstrated that stem cells from different sources have the potential to transform into cardiomyocytes. Human peripheral blood CD34+ cells were transplanted into the hearts of mice with severe combined immune deficiency syndrome, and it was demonstrated that human stem cells could transform into cardiomyocytes, endothelial cells and smooth muscle cells. Using single cell preparation, cell sorting and fluorescent in situ hybridization, human peripheral blood CD34+ cells were transformed into cardiomyocytes mainly through cell fusion, whereas endothelial cells were derived through direct differentiation of the transplanted stem cells. This analytical method should provide a novel approach to identifying the mechanisms of stem cell transformation into cardiomyocytes in vivo.Key Words: Cardiac repair; CD34; Fusion; Stem cell Une démarche novatrice pour étudier la transformation de cellules souches humaines en cellules cardiaques in vivo La greffe de cellules souches a été proposée comme démarche novatrice pour régénérer le myocarde après des dommages cardiaques. De nombreux laboratoires ont démontré que les cellules souches de diverses sources peuvent se transformer en cardiomyocytes. Des cellules CD34+ du sang périphérique humain ont été greffées dans le coeur de souris atteintes d'un syndrome d'immunodéficience combinée sévère, et il a été démontré que les cellules souches pouvaient se transformer en cardiomyocytes, en cellules endothéliales et en cellules des muscles lisses. À l'aide de prépara-tions unicellulaires, de classement cellulaire et d'hybridation in situ en fluorescence, les cellules CD34+ du sang périphérique humain ont été transformées en cardiomyocytes, notamment par fusion cellulaire, tandis que les cellules endothéliales étaient dérivées par différenciation directe des cellules souches greffées. Cette méthode analytique devrait procurer une démarche novatrice pour repérer les mécanismes de transformation des cellules souches en cardiomyocytes in vivo.

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Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle

Cited by 117 publications

References 53 publications

Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function

Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function

Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart

A novel approach to studying the transformation of human stem cells into cardiac cells in vivo

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