Heart regeneration with human pluripotent stem cells: Prospects and challenges

Jiang, Yuqian; Lian, Xiaojun

doi:10.1016/j.bioactmat.2020.01.003

Cited by 27 publications

(19 citation statements)

References 108 publications

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“…For the repair methods, non-cardiomyocytes [25,26], cardiac-derived cells [27,28], and pluripotent stem cells [29,30]are differentiated into functional myocardial cells by transplantation in vivo, thereby improving the function of the heart. However, results showed that these cells rarely differentiate into cardiomyocytes in the body and may cause negative effects such as arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Wang

et al. 2020

Preprint

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Mammal cardiomyocytes lose their ability of regeneration shortly after birth. Reduced cardiomyocytes number caused by myocardial damage is unable to reverse in current clinical therapies. Therefore, it is important and urgent to find new approaches to stimulate cardiomyocytes regeneration. Here we design a recombinant protein IGF1-24 and show that it triggers cardiomyocytes proliferation in rat. 7 days after tail intravenous injection of IGF1-24 ， 6-7-weeks-old healthy rats showed marked improvements in cardiomyocytes proliferation. Next, we injured rats cardiac with isoproterenol and treated them with IGF1-24 injection. We found that it efficiently induced cell proliferation with significant improvements in heart histology. These results show that the recombinant IGF1-24 stimulates cardiomyocytes proliferation and can be used to achieve cardiac repair through stimulating endogenous cardiomyocyte proliferation in rats. The IGF 1-24 could be a prospective medicine to heart repair because it has high efficiency in triggering cell proliferation and it can be easily applied to heart by intravenous injection

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Section: Discussionmentioning

confidence: 99%

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Wang

et al. 2020

Preprint

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“…Unlike adult stem cells, PSCs are highly expandable and can virtually differentiate into any adult somatic cell types, providing an unlimited source of cardiomyocytes. Numerous differentiation techniques have been developed to induce CMs from PSCs [64]. The initial differentiation method involved the embryoid body (EB) formation.…”

Section: Pluripotent Stem Cell-derived Cardiomyocytes Human Es-derivementioning

confidence: 99%

Mending a broken heart: current strategies and limitations of cell-based therapy

Liew

Soh

2020

Stem Cell Res Ther

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The versatility of pluripotent stem cells, attributable to their unlimited self-renewal capacity and plasticity, has sparked a considerable interest for potential application in regenerative medicine. Over the past decade, the concept of replenishing the lost cardiomyocytes, the crux of the matter in ischemic heart disease, with pluripotent stem cell-derived cardiomyocytes (PSC-CM) has been validated with promising pre-clinical results. Nevertheless, clinical translation was hemmed in by limitations such as immature cardiac properties, long-term engraftment, graft-associated arrhythmias, immunogenicity, and risk of tumorigenicity. The continuous progress of stem cell-based cardiac therapy, incorporated with tissue engineering strategies and delivery of cardio-protective exosomes, provides an optimistic outlook on the development of curative treatment for heart failure. This review provides an overview and current status of stem cell-based therapy for heart regeneration, with particular focus on the use of PSC-CM. In addition, we also highlight the associated challenges in clinical application and discuss the potential strategies in developing successful cardiac-regenerative therapy.

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“…In the first step, stem cells are differentiated into cardiac mesoderm via the introduction of Activin A, bone morphogenetic protein 4, FGF2, VEGF, and Wnt/β-catenin factors [ 109 , 110 ]. Then, the cells are exposed to dickkopf homolog 1 (DKK1) or the inhibitors of Wnt/β-catenin and Activin/Nodal to transform them into cardiac progenitors [ 111 , 112 ]. Lastly, the cells are differentiated into cardiomyocytes and induced to proliferate through the regulation of HGF, platelet-derived growth factor, Neuregulin-1, Notch-1, and Wnt/β-catenin [ 60 , 112 ].…”

Section: Genetically Modified Stem Cell For MI Treatmentmentioning

confidence: 99%

“…An enhanced expression of VEGF in vascular endothelial cells following MI contributes to angiogenesis via the increased reactive oxygen species and endoplasmic reticulum stress-mediated autophagy [ 124 ]. Moreover, the differentiation of PSCs into endothelial cells is regulated similarly to cardiomyocyte factors, such as bone morphogenetic protein 4, Activin A, VEGF, and bFGF, due to a shared signaling pathway in cardiogenic or hemogenic mesoderm [ 111 ]. In general, the number of cardiomyocytes decreased in the infarcted heart and lost their proliferation abilities in vivo.…”

Section: Genetically Modified Stem Cell For MI Treatmentmentioning

confidence: 99%

Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

Raziyeva

Smagulova

Kim

et al. 2020

IJMS

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Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction. However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells. Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application. In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents. Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well.

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Heart regeneration with human pluripotent stem cells: Prospects and challenges

Cited by 27 publications

References 108 publications

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Mending a broken heart: current strategies and limitations of cell-based therapy

Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

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