Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types

Singla, Dinender K.; Hacker, Timothy A.; Ma, Lining; Douglas, Pamela S.; Sullivan, Ruth; Lyons, Gary E.; Kamp, Timothy J.

doi:10.1016/j.yjmcc.2005.09.001

Cited by 145 publications

(151 citation statements)

References 12 publications

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“…The apparent independence from oxidative metabolism observed in our study positions embryonic stem cells as ideal candidates for survival and differentiation in an energetically challenging environment, such as the infarcted myocardium, providing a basis for their use in cardiac repair. 2,4,9,10,21 Compared to the embryonic source, derived cardiomyocytes displayed a divergent expression pattern of genes, with nonmuscle and cardiac-muscle-specific metabolic enzyme isoforms, respectively, down-and upregulated. Besides regulating cardiac differentiation, the increased expression of cardiac transcription factors promotes mitochondrial function and cellular organization.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells

Chung¹,

Dzeja²,

Faustino³

et al. 2007

Nat Rev Cardiol

465

482

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SUMMARYCardiogenesis within embryos or associated with heart repair requires stem cell differentiation into energetically competent, contracting cardiomyocytes. While it is widely accepted that the coordination of genetic circuits with developmental bioenergetics is critical to phenotype specification, the metabolic mechanisms that drive cardiac transformation are largely unknown. Here, we aim to define the energetic requirements for and the metabolic microenvironment needed to support the cardiac differentiation of embryonic stem cells. We demonstrate that anaerobic glycolytic metabolism, while sufficient for embryonic stem cell homeostasis, must be transformed into the more efficient mitochondrial oxidative metabolism to secure cardiac specification and excitation-contraction coupling. This energetic switch was programmed by rearrangement of the metabolic transcriptome that encodes components of glycolysis, fatty acid oxidation, the Krebs cycle, and the electron transport chain. Modifying the copy number of regulators of mitochondrial fusion and fission resulted in mitochondrial maturation and network expansion, which in turn provided an energetic continuum to supply nascent sarcomeres. Disrupting respiratory chain function prevented mitochondrial organization and compromised the energetic infrastructure, causing deficient sarcomerogenesis and contractile malfunction. Thus, establishment of the mitochondrial system and engagement of oxidative metabolism are prerequisites for the differentiation of stem cells into a functional cardiac phenotype. Mitochondria-dependent energetic circuits are thus critical regulators of de novo cardiogenesis and targets for heart regeneration.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells

Chung¹,

Dzeja²,

Faustino³

et al. 2007

Nat Rev Cardiol

465

482

View full text Add to dashboard Cite

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“…Finally, we tested the function of the human pluripotent stem cell-derived AECs in a mouse model of myocardial infarction (32,33). To induce myocardial infarction, the left coronary artery was permanently ligated.…”

Section: Molecular and Functional Characterization Of Endothelial Cellsmentioning

confidence: 99%

Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

Zhang

Chu

Hou

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

106

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Here, we report the derivation of arterial endothelial cells from human pluripotent stem cells that exhibit arterial-specific functions in vitro and in vivo. We combine single-cell RNA sequencing of embryonic mouse endothelial cells with an EFNB2-tdTomato/ EPHB4-EGFP dual reporter human embryonic stem cell line to identify factors that regulate arterial endothelial cell specification. The resulting xeno-free protocol produces cells with gene expression profiles, oxygen consumption rates, nitric oxide production levels, shear stress responses, and TNFα-induced leukocyte adhesion rates characteristic of arterial endothelial cells. Arterial endothelial cells were robustly generated from multiple human embryonic and induced pluripotent stem cell lines and have potential applications for both disease modeling and regenerative medicine.arterial endothelial cells | arterial-specific functions | myocardial infarction | single-cell RNA-seq | human pluripotent stem cell differentiation

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“…16 Animal studies using ESC demonstrated cardiomyocyte differentiation and improved ventricular function. 17 These findings spurred development of ESC-like cells by reprogramming adult cells to become undifferentiated pluripotent cells for autologous transplantation, known as induced pluripotent stem cells (iPSC). Preclinical studies showed temporary benefits on remodeling and function, but teratoma concerns remain.…”

Section: Cell Typesmentioning

confidence: 99%

Stem Cell Therapy for Heart Disease

2013

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Coronary artery disease is the leading cause of death in Americans. After myocardial infarction, significant ventricular damage persists despite timely reperfusion and pharmacological management. Treatment is limited, as current modalities do not cure this damage. In the past decade, stem cell therapy has emerged as a promising therapeutic solution to restore myocardial function. Clinical trials have demonstrated safety and beneficial effects in patients suffering from acute myocardial infarction, heart failure, and dilated cardiomyopathy. These benefits include improved ventricular function, increased ejection fraction, and decreased infarct size. Mechanisms of therapy are still not clearly understood. However, it is believed that paracrine factors, including stromal cell-derived factor-1, contribute significantly to stem cell benefits. The purpose of this article is to provide medical professionals with an overview on stem cell therapy for the heart and to discuss potential future directions.

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Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types

Cited by 145 publications

References 12 publications

Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells

Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells

Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

Stem Cell Therapy for Heart Disease

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