Journal ArticleDOI
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.
Nicola Smart,Catherine A. Risebro,Athalie A. D. Melville,Kelvin A. Moses,Robert J. Schwartz,Kenneth R. Chien,Paul R. Riley +6 more
TLDR
Thymosin β4 (Tβ4) is identified as essential for all aspects of coronary vessel development in mice, and it is demonstrated that Tβ4 stimulates significant outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation of fibroblasts, smooth muscle cells and endothelial cells.Abstract:
Cardiac failure has a principal underlying aetiology of ischaemic damage arising from vascular insufficiency. Molecules that regulate collateral growth in the ischaemic heart also regulate coronary vasculature formation during embryogenesis. Here we identify thymosin beta4 (Tbeta4) as essential for all aspects of coronary vessel development in mice, and demonstrate that Tbeta4 stimulates significant outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation of fibroblasts, smooth muscle cells and endothelial cells. Tbeta4 knockdown in the heart is accompanied by significant reduction in the pro-angiogenic cleavage product N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Although injection of AcSDKP was unable to rescue Tbeta4 mutant hearts, it significantly enhanced endothelial cell differentiation from adult epicardially derived precursor cells. This study identifies Tbeta4 and AcSDKP as potent stimulators of coronary vasculogenesis and angiogenesis, and reveals Tbeta4-induced adult epicardial cells as a viable source of vascular progenitors for continued renewal of regressed vessels at low basal level or sustained neovascularization following cardiac injury.read more
Citations
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Journal ArticleDOI
Stem-cell therapy for cardiac disease
TL;DR: In conclusion, resident cardiac stem cells have been shown to differentiate into multiple cell types present in the heart, including cardiac muscle cells, indicating that the heart is not terminally differentiated.
Journal ArticleDOI
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Li Qian,Yu Huang,C. Ian Spencer,Amy Foley,Vasanth Vedantham,Lei Liu,Simon J. Conway,Ji-Dong Fu,Deepak Srivastava +8 more
TL;DR: In this article, the authors used genetic lineage tracing to show that resident nonmyocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation.
Journal ArticleDOI
25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine
Nasim Annabi,Nasim Annabi,Ali Tamayol,Ali Tamayol,Jorge Alfredo Uquillas,Jorge Alfredo Uquillas,Mohsen Akbari,Mohsen Akbari,Luiz E. Bertassoni,Luiz E. Bertassoni,Chaenyung Cha,Chaenyung Cha,Gulden Camci-Unal,Gulden Camci-Unal,Mehmet R. Dokmeci,Mehmet R. Dokmeci,Nicholas A. Peppas,Ali Khademhosseini,Ali Khademhosseini +18 more
TL;DR: The development of advanced hydrogel with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels, and a number of potential applications and challenges in the utilization in regenerative medicine are reviewed.
Journal Article
Abstract 10466: In Vivo Reprogramming of Murine Cardiac Fibroblasts into Induced Cardiomyocytes
Li Qian,Yu Huang,Amy Foley,Vasanth Vedantham,Ian Spencer,Simon J. Conway,Ji-Dong Fu,Deepak Srivastava +7 more
TL;DR: It is shown 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 and delivery of the pro-angiogenic and fibroblast-activating peptides resulted in further improvements in scar area and cardiac function.
Journal ArticleDOI
Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
Bin Zhou,Qing Ma,Qing Ma,Satish Rajagopal,Satish Rajagopal,Sean M. Wu,Ibrahim J. Domian,José Rivera-Feliciano,Dawei Jiang,Alexander von Gise,Alexander von Gise,Alexander von Gise,Sadakatsu Ikeda,Sadakatsu Ikeda,Kenneth R. Chien,William T. Pu,William T. Pu +16 more
TL;DR: A novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium—an epithelial sheet overlying the heart is identified and identified as previously unrecognized cardiomyocyte progenitors.
References
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Coronary Artery Anomalies An Entity in Search of an Identity
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Journal ArticleDOI
Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair
TL;DR: It is shown that the G-actin sequestering peptide thymosin β4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes and that the pathway it regulates may be a new therapeutic target in the setting of acute myocardIAL damage.