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Article: Generation of Induced Cardiospheres via Reprogramming of Skin Fibroblasts for Myocardial Regeneration

TitleGeneration of Induced Cardiospheres via Reprogramming of Skin Fibroblasts for Myocardial Regeneration
Authors
KeywordsSkin fibroblast
Cardiac progenitor cells
Myocardial regeneration
Cardiospheres
Somatic reprogramming
Issue Date2016
PublisherAlphaMed Press, Inc. The Journal's web site is located at http://www.stemcells.com
Citation
Stem Cells, 2016, v. 34, n. 11, p. 2693-2706 How to Cite?
Abstract© 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed PressRecent pre-clinical and clinical studies have suggested that endogenous cardiospheres (eCS) are potentially safe and effective for cardiac regeneration following myocardial infarction (MI). Nevertheless the preparation of autologous eCS requires invasive myocardial biopsy with limited yield. We describe a novel approach to generate induced cardiospheres (iCS) from adult skin fibroblasts via somatic reprogramming. After infection with Sox2, Klf4, and Oct4, iCS were generated from mouse adult skin fibroblasts treated with Gsk3β inhibitor-(2′Z,3′E)- 6-Bromoindirubin-3′-oxime and Oncostatin M. They resembled eCS, but contained a higher percentage of cells expressing Mesp1, Isl1, and Nkx2.5. They were differentiated into functional cardiomyocytes in vitro with similar electrophysiological properties, calcium transient and contractile function to eCS and mouse embryonic stem cell-derived cardiomyocytes. Transplantation of iCS (1 × 106 cells) into mouse myocardium following MI had similar effects to transplantation of eCS but significantly better than saline or fibroblast in improving left ventricular ejection fraction, increasing anterior/septal ventricular wall thickness and capillary density in the infarcted region 4 weeks after transplantation. No tumor formation was observed. iCS generated from adult skin fibroblasts by somatic reprogramming and a cocktail of Gsk3β inhibitor-6-Bromoindirubin-3′-oxime and Oncostatin M may represent a novel source for cell therapy in MI. Stem Cells 2016;34:2693–2706.
Persistent Identifierhttp://hdl.handle.net/10722/238153
ISSN
2023 Impact Factor: 4.0
2023 SCImago Journal Rankings: 1.396
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXu, Jian Yong-
dc.contributor.authorLee, Yee Ki-
dc.contributor.authorRan, Xinru-
dc.contributor.authorLiao, Song Yan-
dc.contributor.authorYang, Jiayin-
dc.contributor.authorAu, Ka Wing-
dc.contributor.authorLai, Wing Hon-
dc.contributor.authorEsteban, Miguel A.-
dc.contributor.authorTse, Hung Fat-
dc.date.accessioned2017-02-03T02:13:13Z-
dc.date.available2017-02-03T02:13:13Z-
dc.date.issued2016-
dc.identifier.citationStem Cells, 2016, v. 34, n. 11, p. 2693-2706-
dc.identifier.issn1066-5099-
dc.identifier.urihttp://hdl.handle.net/10722/238153-
dc.description.abstract© 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed PressRecent pre-clinical and clinical studies have suggested that endogenous cardiospheres (eCS) are potentially safe and effective for cardiac regeneration following myocardial infarction (MI). Nevertheless the preparation of autologous eCS requires invasive myocardial biopsy with limited yield. We describe a novel approach to generate induced cardiospheres (iCS) from adult skin fibroblasts via somatic reprogramming. After infection with Sox2, Klf4, and Oct4, iCS were generated from mouse adult skin fibroblasts treated with Gsk3β inhibitor-(2′Z,3′E)- 6-Bromoindirubin-3′-oxime and Oncostatin M. They resembled eCS, but contained a higher percentage of cells expressing Mesp1, Isl1, and Nkx2.5. They were differentiated into functional cardiomyocytes in vitro with similar electrophysiological properties, calcium transient and contractile function to eCS and mouse embryonic stem cell-derived cardiomyocytes. Transplantation of iCS (1 × 106 cells) into mouse myocardium following MI had similar effects to transplantation of eCS but significantly better than saline or fibroblast in improving left ventricular ejection fraction, increasing anterior/septal ventricular wall thickness and capillary density in the infarcted region 4 weeks after transplantation. No tumor formation was observed. iCS generated from adult skin fibroblasts by somatic reprogramming and a cocktail of Gsk3β inhibitor-6-Bromoindirubin-3′-oxime and Oncostatin M may represent a novel source for cell therapy in MI. Stem Cells 2016;34:2693–2706.-
dc.languageeng-
dc.publisherAlphaMed Press, Inc. The Journal's web site is located at http://www.stemcells.com-
dc.relation.ispartofStem Cells-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSkin fibroblast-
dc.subjectCardiac progenitor cells-
dc.subjectMyocardial regeneration-
dc.subjectCardiospheres-
dc.subjectSomatic reprogramming-
dc.titleGeneration of Induced Cardiospheres via Reprogramming of Skin Fibroblasts for Myocardial Regeneration-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/stem.2438-
dc.identifier.pmid27333945-
dc.identifier.scopuseid_2-s2.0-84978224425-
dc.identifier.hkuros263950-
dc.identifier.volume34-
dc.identifier.issue11-
dc.identifier.spage2693-
dc.identifier.epage2706-
dc.identifier.eissn1549-4918-
dc.identifier.isiWOS:000387034000008-
dc.publisher.placeUnited States-
dc.customcontrol.immutablecsl 170206-
dc.identifier.issnl1066-5099-

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