Cofilin-2 regulates the actin cytoskeleton by promoting conversion of polymerized F-Actin back into monomeric G-Actin ( Torrini et al., 2019 ); we then assessed the ratio between G-Actin and F-Actin in treated mNVCM; cells stimulated by fetal hAFSC-EVs showed a mild trend in the increase of polymerized F-Actin compared to the monomeric G form, as evaluated by the F/G ratio fold change ( Figure 3C ). 3.3 Fetal hAFSC-EVs can Sustain Resident Cardiomyocyte Cell Cycle Progression in a Preclinical Neonatal Mouse Model of Myocardial Infarction in the Short Term The cardioactive paracrine potential of fetal hAFSC-EVs was evaluated in a 4-day-old (P4) and 7-day-old (P7) R26FUCCI2 +/− neonatal mouse model of myocardial infarction (MI), at 3 and 7 days post injury.
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Investigating the Paracrine Role of Perinatal Derivatives: Human Amniotic Fluid Stem Cell-Extracellular Vesicles Show Promising Transient Potential for Cardiomyocyte Renewal.
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Stimulating primary neonatal cardiomyocytes with fetal hAFSC-EVs in combination with the YAP inhibitor Verteporfin ( Bassat et al., 2017 ) resulted in a negative trend of their cell cycle re-entry.
The presence of the YAP inhibitor during hAFSC-EV treatment resulted in a decreasing trend of cardiogenic effect by about 40%, suggesting a possible, yet mild, putative involvement of YAP signaling in the hAFSC-EV paracrine mechanism ( Figure 6B ). 4 Discussion This study shows that immature fetal hAFSC obtained from leftover samples of II trimester prenatal diagnosis amniocentesis secrete extracellular vesicles as their most cardioactive secretome formulation to support cell cycle re-entry and proliferation of murine cardiomyocytes.
Treated mNVCM showed disorganized expression of cardiac alpha-actinin, suggesting cytoskeletal re-arrangements prior to cell renewal, with a 40% significant downregulation of Cofilin-2 and a positive trend of polymerized F-Actin.