Pleiotropic effects of extracellular vesicles from induced pluripotent stem cell–derived cardiomyocytes on ischemic cardiomyopathy: A preclinical study

Tominaga, Yuji; Kawamura, Takuji; Ito, Emiko; Takeda, Maki; Harada, Akima; Torigata, Kosuke; Sakaniwa, Ryoto; Sawa, Yoshiki; Miyagawa, Shigeru

doi:10.1016/j.healun.2023.08.011

Cited by 10 publications

(3 citation statements)

References 43 publications

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“…Another emerging application for EVs consists in their use as pharmacological vectors. EVs isolated from induced pluripotent stem cell-derived cardiomyocytes contained miRNA and proteins associate with angiogenesis, antifibrosis, promotion of M2 macrophage polarization, cell proliferation, and anti-apoptosis [ 71 ]. EVs are esteemed as promising delivery vehicles for a diverse range of genetic therapeutics, as they can be loaded with molecules either naturally, during their biogenesis, or following EV isolation using physical or chemical methods [ 72 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Extracellular vesicles in cardiomyopathies: A narrative review

Rizzuto,

Faggiano,

Macchi

et al. 2024

Heliyon

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Section: Future Perspectivesmentioning

confidence: 99%

Extracellular vesicles in cardiomyopathies: A narrative review

Rizzuto,

Faggiano,

Macchi

et al. 2024

Heliyon

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“…hiPSC-CMs are increasingly recognized as a relevant in vitro model to study human cardiomyocyte biology. In addiZon, these cells release EVs 12,13,15,19,[40][41][42][43][44][45][46] , although the variaZons in the heterogeneity of these EVs remain unclear. The protocol applied here 47 enabled the generaZon of a pure populaZon of beaZng cardiomyocytes (Figure S1, Video S1).…”

Section: Hipsc-derived Cardiomyocytes (Hipsc-cms) Secrete Small Extra...mentioning

confidence: 99%

“…8 Finally, CM-EVs released by human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have therapeuZc potenZal for treaZng MI. Preclinical studies in rodents showed that these EVs improved heart funcZon when injected directly into infarcted hearts [12][13][14] or delivered in a hydrogel. 15,16 EVs are a heterogeneous group of vesicles of different sizes, ranging from 50 nm to several µm in size, which are produced through various biogenesis mechanisms.…”

Section: Introduc2onmentioning

confidence: 99%

Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes

Viola,

Bebelman,

Maas

et al. 2024

Preprint

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Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters. These modified hiPSC-CMs allow for robust quantification of CM-EV secretion from small numbers of cells without the need for time-consuming EV isolation techniques. We subjected these cells to a panel of small molecules to study their effect on CM-EV biogenesis and secretion under basal and stress-associated conditions. We observed that EV biogenesis is context-dependent in hiPSC-CMs. Nutrient starvation decreases CM-EV secretion while hypoxia increases the production of CM-EVs in a nSmase2-dependent manner. Moreover, the inflammatory cytokine TNF-α increased CM-EV secretion through a process involving NLRP3 inflammasome activation and mTOR signaling. Here, we detailed for the first time the regulatory mechanisms of EV biogenesis in hiPSC-CMs upon MI-associated stressors.

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Hypoxia and TNF‐alpha modulate extracellular vesicle release from human induced pluripotent stem cell‐derived cardiomyocytes

Viola,

Bebelman,

Maas

et al. 2024

J of Extracellular Vesicle

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Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte‐derived EV (CM‐EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) that express NanoLuc‐tetraspanin reporters. These modified hiPSC‐CMs allow for quantification of tetraspanin‐positive CM‐EV secretion from small numbers of cells without the need for time‐consuming EV isolation techniques. We subjected these cells to a panel of small molecules to study their effect on CM‐EV biogenesis and secretion under basal and stress‐associated conditions. We observed that EV biogenesis is context‐dependent in hiPSC‐CMs. Nutrient starvation decreases CM‐EV secretion while hypoxia increases the production of CM‐EVs in a nSmase2‐dependent manner. Moreover, the inflammatory cytokine TNF‐α increased CM‐EV secretion through a process involving NLRP3 inflammasome activation and mTOR signalling. Here, we detailed for the first time the regulatory mechanisms of EV biogenesis in hiPSC‐CMs upon MI‐associated stressors.

show abstract

Pleiotropic effects of extracellular vesicles from induced pluripotent stem cell–derived cardiomyocytes on ischemic cardiomyopathy: A preclinical study

Cited by 10 publications

References 43 publications

Extracellular vesicles in cardiomyopathies: A narrative review

Extracellular vesicles in cardiomyopathies: A narrative review

Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes

Hypoxia and TNF‐alpha modulate extracellular vesicle release from human induced pluripotent stem cell‐derived cardiomyocytes

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