Mesenchymal stem cells suppress cardiac alternans by activation of PI3K mediated nitroso-redox pathway

Sattayaprasert, Prasongchai; Nassal, Drew; Wan, Xiaoping; Deschênes, Isabelle; Laurita, Kenneth R.

doi:10.1016/j.yjmcc.2016.05.014

Cited by 10 publications

(11 citation statements)

References 51 publications

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“…53 Sattayaprasert et al further showed that hMSC conditioned media reduces calcium transient alternans and shortens calcium transient duration in hydrogen peroxide treated human induced pluripotent stem cell derived-cardiac myocyte monolayers. 55 Similarly, mouse MSC conditioned media attenuated the occurrence of arrhythmic calcium transients of ischemia/reperfusion injured isolated ventricular myocytes. 56 Thus, across species, hMSC conditioned media appears to have favorable effects on calcium handling in cultured cardiomyocytes.…”

Section: Stem Cell Secretomes Can Impact Cardiomyocyte Eccmentioning

confidence: 98%

“…51 On the other hand, in hydrogen peroxide treated human induced pluripotent stem cell derived-cardiac myocyte monolayers, hMSC conditioned media significantly decreased action potential alternans relative to control. 55…”

Section: Stem Cell Secretomes Can Impact Cardiomyocyte Eccmentioning

confidence: 99%

“…54 This signaling pathway was also implicated in MSC paracrine-mediated cardioprotection from ischemia/reperfusion injury in vitro, where hMSC conditioned Tyrode’s solution attenuated the hyperpolarization of the mitochondrial membrane potential via PI3K/Akt signaling 56 , prolonging cell survival and reducing arrhythmic early after depolarizations. The role of the PI3K/Akt signaling pathway in hMSC conditioned media-mediated ECC enhancement was further defined in human induced pluripotent stem cell-derived cardiomyocyte calcium handling by Sattayaprasert et al, 55 where inhibitors of PI3K and endothelial nitric oxide synthase (a downstream mediator of PI3K) attenuated the benefits of hMSC paracrine media on calcium transient alternans and duration, whereas S-nitrosoglutathione, an nitric oxide donor, had opposite effects. Taken together, these findings confirm that the PI3K/AKT pathway is a critical mediator of the effects of hMSC paracrine factors on cardiomyocyte ECC.…”

Section: Stem Cell Secretomes Can Impact Cardiomyocyte Eccmentioning

confidence: 99%

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Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling

Mayourian

Ceholski

Gonzalez

et al. 2018

Circulation Research

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Cardiac excitation-contraction coupling (ECC) is the orchestrated process of initial myocyte electrical excitation, which leads to calcium entry, intracellular trafficking, and subsequent sarcomere shortening and myofibrillar contraction. Neurohumoral β-adrenergic signaling is a well-established mediator of ECC; other signaling mechanisms, such as paracrine signaling, have also demonstrated significant impact on ECC but are less well understood. For example, resident heart endothelial cells are well-known physiological paracrine modulators of cardiac myocyte ECC mainly via NO and endothelin-1. Moreover, recent studies have demonstrated other resident noncardiomyocyte heart cells (eg, physiological fibroblasts and pathological myofibroblasts), and even experimental cardiotherapeutic cells (eg, mesenchymal stem cells) are also capable of altering cardiomyocyte ECC through paracrine mechanisms. In this review, we first focus on the paracrine-mediated effects of resident and therapeutic noncardiomyocytes on cardiomyocyte hypertrophy, electrophysiology, and calcium handling, each of which can modulate ECC, and then discuss the current knowledge about key paracrine factors and their underlying mechanisms of action. Next, we provide a case example demonstrating the promise of tissue-engineering approaches to study paracrine effects on tissue-level contractility. More specifically, we present new functional and molecular data on the effects of human adult cardiac fibroblast conditioned media on human engineered cardiac tissue contractility and ion channel gene expression that generally agrees with previous murine studies but also suggests possible species-specific differences. By contrast, paracrine secretions by human dermal fibroblasts had no discernible effect on human engineered cardiac tissue contractile function and gene expression. Finally, we discuss systems biology approaches to help identify key stem cell paracrine mediators of ECC and their associated mechanistic pathways. Such integration of tissue-engineering and systems biology methods shows promise to reveal novel insights into paracrine mediators of ECC and their underlying mechanisms of action, ultimately leading to improved cell-based therapies for patients with heart disease.

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Section: Stem Cell Secretomes Can Impact Cardiomyocyte Eccmentioning

confidence: 98%

Section: Stem Cell Secretomes Can Impact Cardiomyocyte Eccmentioning

confidence: 99%

Section: Stem Cell Secretomes Can Impact Cardiomyocyte Eccmentioning

confidence: 99%

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Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling

Mayourian

Ceholski

Gonzalez

et al. 2018

Circulation Research

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“…Co-culturing cells, namely on a Transwell insert within a companion plate, is a well-established model to investigate cell-cell interactions in vitro (Sattayaprasert et al, 2016, Heiss et al, 2015. As described in the methods section, two co-culture approaches were used in this study.…”

Section: Hl-1 Cell-endothelial Cell Co-culture Systemmentioning

confidence: 99%

Endothelial cell modulation of cardiomyocyte gene expression

Jiang

Mohr

Ullrich

et al. 2019

Experimental Cell Research

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WB Western blot WGA Wheat germ agglutinin β-MHC -Myosin heavy chain 2013, Fredriksen et al., 2001). Kidney disease is commonly found in heart failure (HF) patients (Grande et al., 2017). It was found that GFR is associated with the degree of cardiac diastolic dysfunction and adverse clinical outcomes (Jain et al., 2017). A recent nationwide population-based cohort study showed that heart failure patients have a higher risk of developing dementia (Adelborg et al., 2017). Studies also revealed post-mortem that 73.6% ± 7.0% of all cardiomyocytes were mono-nucleated, 25.5% ± 7.4% were bi-nucleated, and 1.0% ± 1.2% were tri-nucleated in the heart of individuals aged one month to 73 years. In agreement with previous studies (Mollova et al., 2013, Olivetti et al., 1996), they established that already 1 month after birth; the final number of cardiomyocytes was reached (3.2 ± 0.75 × 10 9 cells) and remained constant throughout life. By stereological measuring the average volume of cardiomyocytes at different ages, it was found that the adaptive about 3-fold greater (endothelium-derived contracting factors) (Flammer et al., 2012). Furchgott and Zawadzki (Furchgott and Zawadzki, 1980) first described the phenomenon of endothelium-dependent relaxation in 1980. Subsequently, the identification of nitric oxide (NO) as the crucial endothelium-derived mediator of vascular relaxation led to substantial progress in cardiovascular research (Flammer et al., 2012). In addition to with arterial hypertension and echocardiographically documented left ventricular hypertrophy, who received either the AT 1 receptor blocker losartan or the β 1 receptor blocker atenolol, were much less likely to experience such a major cardiovascular event (Kjeldsen et al., 2002). Also whereby NT-proBNP levels are more sensitive and specific to distinguish HF from non-HF subjects (Fonseca et al., 2004). NT-proBNP levels were also suggested to be highly predictive of incident atrial fibrillation, the most common cardiac rhythm abnormality, after adjustment for an extensive number of covariates (Patton et al., 2009). Although ANP and BNP have been recommended to provide prognostic information

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“…Numerous studies have shown the regenerative potential of MSCs to counteract organ failures (Xing et al, 2014 ; Desando et al, 2016 ; Sattayaprasert et al, 2016 ). It has also been demonstrated that injecting MSC conditioned medium and not the cells themselves can induce the same effects.…”

Section: Introductionmentioning

confidence: 99%

How Do Mesenchymal Stem Cells Influence or Are Influenced by Microenvironment through Extracellular Vesicles Communication?

Dostert

Mesure

et al. 2017

Front. Cell Dev. Biol.

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Mesenchymal stem cells (MSCs) are widely used in cell therapy and tissue engineering thanks to their self-renewal, their multipotency, and their immunomodulatory properties that make them an attractive tool for regenerative medicine. A large part of MSCs positive effects is due to their secretion products which participate in creating a favorable microenvironment and closely relate these cells to other cell types. Extracellular vesicles (EVs) belong to cellular secretions. They are produced by cells continuously or after stimulation (e.g., calcium flux, cellular stress) and act in tissue homeostasis and intercellular communication. The understanding of the role of EVs is growing, more particularly their impact on cell migration, differentiation, or immunomodulation. EVs derived from MSCs show these interesting properties that may be considered in therapeutics, although they can have adverse effects by facilitating cancer propagation. Moreover, MSC behavior may also be influenced (proliferation, differentiation) by EVs derived from other donor cells. The aim of this mini review is to summarize the two-way communication between MSCs and other cell types, and how they can affect each other with their microenvironment through EVs. On the one hand, the manuscript presents the influence of MSC-derived EVs on diverse recipient cells and on the other hand, the effects of EVs derived from various donor cells on MSCs. The discrepancies between cancer cells and MSCs communication according to the sources of MSCs but also the tumor origins are also mentioned.

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Mesenchymal stem cells suppress cardiac alternans by activation of PI3K mediated nitroso-redox pathway

Cited by 10 publications

References 51 publications

Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling

Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling

Endothelial cell modulation of cardiomyocyte gene expression

How Do Mesenchymal Stem Cells Influence or Are Influenced by Microenvironment through Extracellular Vesicles Communication?

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