Harnessing the Induction of Cardiomyocyte Proliferation for Cardiac Regenerative Medicine

Sharma, Arun; Zhang, Yuan; Wu, Sean M.

doi:10.1007/s11936-015-0404-z

Cited by 19 publications

(17 citation statements)

References 57 publications

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“…To this end, several screening studies have been reported in zebrafish, mouse, and rat systems, revealing novel regulators of cardiomyocyte proliferation (comprehensively reviewed in reference 10 ). Zebrafish studies, using a genetically encoded cell cycle reporter (FUCCI), screened kinase inhibitors to identify Hedgehog (Hh), insulin-like growth factor (IGF) and transforming growth factor-β (TGF- β) as being involved in cardiomyocyte proliferation 11 .…”

mentioning

confidence: 99%

Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays

Titmarsh

Glass

Mills

et al. 2016

Sci Rep

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Inducing cardiomyocyte proliferation in post-mitotic adult heart tissue is attracting significant attention as a therapeutic strategy to regenerate the heart after injury. Model animal screens have identified several candidate signalling pathways, however, it remains unclear as to what extent these pathways can be exploited, either individually or in combination, in the human system. The advent of human cardiac cells from directed differentiation of human pluripotent stem cells (hPSCs) now provides the ability to interrogate human cardiac biology in vitro, but it remains difficult with existing culture formats to simply and rapidly elucidate signalling pathway penetrance and interplay. To facilitate high-throughput combinatorial screening of candidate biologicals or factors driving relevant molecular pathways, we developed a high-density microbioreactor array (HDMA) – a microfluidic cell culture array containing 8100 culture chambers. We used HDMAs to combinatorially screen Wnt, Hedgehog, IGF and FGF pathway agonists. The Wnt activator CHIR99021 was identified as the most potent molecular inducer of human cardiomyocyte proliferation, inducing cell cycle activity marked by Ki67, and an increase in cardiomyocyte numbers compared to controls. The combination of human cardiomyocytes with the HDMA provides a versatile and rapid tool for stratifying combinations of factors for heart regeneration.

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mentioning

confidence: 99%

Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays

Titmarsh

Glass

Mills

et al. 2016

Sci Rep

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“…Although promising, some concerns arise from these studies towards clinical translation. While in vitro and small animal testing of this strategy are encouraging, clinical trials may be hindered by the risk of promiscuous or excessive cell replication, resulting in tumorigenesis [ 55 ].…”

Section: The Stem Cell Therapy Approachmentioning

confidence: 99%

Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The Betrothed

Passaro

Testa

Ambrosone

et al. 2017

Stem Cells International

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Cardiovascular diseases represent the first cause of morbidity in Western countries, and chronic heart failure features a significant health care burden in developed countries. Efforts in the attempt of finding new possible strategies for the treatment of CHF yielded several approaches based on the use of stem cells. The discovery of direct cardiac reprogramming has unveiled a new approach to heart regeneration, allowing, at least in principle, the conversion of one differentiated cell type into another without proceeding through a pluripotent intermediate. First developed for cancer treatment, nanotechnology-based approaches have opened new perspectives in many fields of medical research, including cardiovascular research. Nanotechnology could allow the delivery of molecules with specific biological activity at a sustained and controlled rate in heart tissue, in a cell-specific manner. Potentially, all the mediators and structural molecules involved in the fibrotic process could be selectively targeted by nanocarriers, but to date, only few experiences have been made in cardiac research. This review highlights the most prominent concepts that characterize both the field of cardiac reprogramming and a nanomedicine-based approach to cardiovascular diseases, hypothesizing a possible synergy between these two very promising fields of research in the treatment of heart failure.

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“…In the context of the normally exceedingly infrequent incidence of adult cardiomyocyte replication (<1 %), the possibility of inducing resident cardiomyocyte proliferation through modulation of cell cycle reentry represents an alternative strategy to biologically enhance post-infarct myocardial function [20, 21]. While in vitro and small animal testing of this strategy are encouraging, clinical trials to induce cardiomyocyte replication have not yet begun and may potentially be hindered by the risk of promiscuous or excessive cell replication resulting in tumorigenesis [21].…”

Section: Options For Myocardial Regenerationmentioning

confidence: 99%

“…While in vitro and small animal testing of this strategy are encouraging, clinical trials to induce cardiomyocyte replication have not yet begun and may potentially be hindered by the risk of promiscuous or excessive cell replication resulting in tumorigenesis [21]. …”

Section: Options For Myocardial Regenerationmentioning

confidence: 99%

Direct Cardiac Cellular Reprogramming for Cardiac Regeneration

Patel

Mathison

Singh

et al. 2016

Curr Treat Options Cardio Med

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Harnessing the Induction of Cardiomyocyte Proliferation for Cardiac Regenerative Medicine

Cited by 19 publications

References 57 publications

Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays

Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays

Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The Betrothed

Direct Cardiac Cellular Reprogramming for Cardiac Regeneration

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