High glucose suppresses embryonic stem cell differentiation into cardiomyocytes

Yang, Penghua; Chen, Xi; Kaushal, Sunjay; Reece, E. Albert

doi:10.1186/s13287-016-0446-5

Cited by 25 publications

(22 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, our recent research has indicated that high glucose suppresses embryonic stem cell cardiogenesis (26). When glucose-responsive E14 mouse embryonic stem cells (GR-E14 cells) are cultured under high glucose conditions, high glucose prevents the differentiation of GR-E14 cells into contracting cardiomyocytes.…”

Section: Mechanisms Of Maternal Diabetes-induced Chdmentioning

confidence: 99%

“…When glucose-responsive E14 mouse embryonic stem cells (GR-E14 cells) are cultured under high glucose conditions, high glucose prevents the differentiation of GR-E14 cells into contracting cardiomyocytes. Further study has revealed that high glucose represses the expression of essential genes for cardiogenesis, inhibiting the maturation of differentiated cardiomyocytes from GR-E14 cells and reducing potassium channel proteins that are important for cardiomyocyte contraction (26). Similarly, a recent study revealed that pregestational maternal diabetes suppresses the differentiation of murine embryonic D3 stem cells into cardiomyocytes (27).…”

Section: Mechanisms Of Maternal Diabetes-induced Chdmentioning

confidence: 99%

“…Animal studies have indicated that maternal diabetes-induced heart failure (HF) can be characterized by a gradual loss of cardiomyocytes, and experimental inhibition of apoptosis is responsible for improving cardiac function (26,28). The current standard therapy for HF caused by cardiomyocyte loss is heart transplantation (HT) or mechanical circulatory support (29,30).…”

Section: Heart Transplantation and Medical And Device Therapies For Chdmentioning

confidence: 99%

“…Thus prenatal transplantation of CPCs rescues the cardiac dysfunctions (45). Previous studies from our laboratory have indicated that maternal diabetes and high glucose affect stem/progenitor cells in cardiogenesis by suppressing differentiation or inducing cell death (26,28). Therefore, cardiac stem/progenitor cell therapy for maternal diabetes-induced CHD is a possible solution for surgical and medical care challenges.…”

Section: Cardiac Stem/progenitor Cell Therapy For Chdmentioning

confidence: 99%

“…As described above, maternal diabetes causes adverse effects on the biological function of embryonic stem cells and CPCs (26,28). Another recent study has shown that human umbilical cord mesenchymal stromal cells isolated from women with gestational diabetes display premature aging, poorer cell growth, and mitochondrial dysfunction, reducing the therapeutic potential of stem cells (117).…”

Section: Future Directionsmentioning

confidence: 99%

See 4 more Smart Citations

The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pregestational maternal diabetes induces congenital heart defects (CHDs). Cardiac dysfunction after palliative surgical procedures contributes to the high mortality of CHD patients. Autologous or allogeneic stem cell therapies are effective for improving cardiac function in animal models and clinical trials. c-kit+ cardiac progenitor cells (CPCs), the most recognized CPCs, have the following basic properties of stem cells: self-renewal, multicellular clone formation, and differentiation into multiple cardiac lineages. However, there is ongoing debate regarding whether c-kit+ CPCs can give rise to sufficient cardiomyocytes. A new hypothesis to address the beneficial effect of c-kit+ CPCs is that these cells stimulate endogenous cardiac cells through a paracrine function in producing a robust secretome and exosomes. The values of other cardiac CPCs, including Sca1+ CPCs and cardiosphere-derived cells, are beginning to be revealed. These cells may be better choices than c-kit+ CPCs for generating cardiomyocytes. Adult mesenchymal stem cells are considered immune-incompetent and effective for improving cardiac function. Autologous CPC therapy may be limited by the observation that maternal diabetes adversely affects the biological function of embryonic stem cells and CPCs. Future studies should focus on determining the mechanistic action of these cells, identifying new CPC markers, selecting highly effective CPCs, and engineering cell-free products.

show abstract

Section: Mechanisms Of Maternal Diabetes-induced Chdmentioning

confidence: 99%

Section: Mechanisms Of Maternal Diabetes-induced Chdmentioning

confidence: 99%

Section: Heart Transplantation and Medical And Device Therapies For Chdmentioning

confidence: 99%

Section: Cardiac Stem/progenitor Cell Therapy For Chdmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

See 3 more Smart Citations

The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms

Basu

Garg

2018

Birth Defects Research

120

View full text Add to dashboard Cite

Congenital heart disease (CHD) is the most common type of birth defect and is both a significant pediatric and adult health problem, in light of a growing population of survivors. The etiology of CHD has been considered to be multifactorial with genetic and environmental factors playing important roles. The combination of advances in cardiac developmental biology, which have resulted in the elucidation of molecular pathways regulating normal cardiac morphogenesis, and genome sequencing technology have allowed the discovery of numerous genetic contributors of CHD ranging from chromosomal abnormalities to single gene variants. On the other hand, mechanistic details of the contribution of environmental factors to CHD remain unknown. Maternal diabetes mellitus (matDM) is a well-established and increasingly prevalent environmental risk factor for CHD, but the underlying etiologic mechanisms by which pre-gestational matDM increases the vulnerability of embryos to cardiac malformations remains largely elusive. Here, we will briefly discuss the multifactorial etiology of CHD with a focus on the epidemiologic link between matDM and CHD. We will describe the animal models used to study the underlying mechanisms between matDM and CHD and review the numerous cellular and molecular pathways affected by maternal hyperglycemia in the developing heart. Lastly, we discuss how this increased understanding may open the door for the development of novel prevention strategies to reduce the incidence of CHD in this high-risk population.

show abstract

Computational fluid dynamics modeling, a novel, and effective approach for developing scalable cell therapy manufacturing processes

Shafa

Panchalingam

Walsh

et al. 2019

Biotech & Bioengineering

View full text Add to dashboard Cite

Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor-intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high-quality iPSC derivatives under controlled conditions. The current scale-up methods used in cell therapy processes are based on empirical, geometry-dependent methods that do not accurately represent the hydrodynamics of 3D bioreactors. These methods require multiple iterations of scale-up studies, resulting in increased development cost and time. Here we show a novel approach using computational fluid dynamics modeling to effectively scale-up cell therapy manufacturing processes in 3D bioreactors. Using a GMP-compatible iPSC line, we translated and scaled-up a small-scale cardiomyocyte differentiation process to a 3-L computer-controlled bioreactor in an efficient manner, showing comparability in both systems. K E Y W O R D S cardiomyocytes, cGMP, computational fluid dynamics, induced pluripotent stem cells

show abstract

High glucose suppresses embryonic stem cell differentiation into cardiomyocytes

Cited by 25 publications

References 61 publications

The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy

The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy

Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms

Computational fluid dynamics modeling, a novel, and effective approach for developing scalable cell therapy manufacturing processes

Contact Info

Product

Resources

About