Key result
Extracellular vesicles improve LVEF by ~18% post-MI without triggering cardiomyocyte proliferation.
Why the study?
It is unclear whether extracellular vesicles mediate cardiac regeneration through endogenous cardiomyocyte proliferation in chronically infarcted hearts.
Does EV-CPC administration trigger cardiomyocyte proliferation and improve cardiac function in chronically infarcted mouse models?
Does EV-CPC administration trigger cardiomyocyte proliferation and improve cardiac function in chronically infarcted mouse models?
Answers are grounded in this paper and cite their sources.
Extracellular vesicles from cardiovascular progenitor cells improve cardiac function and reduce fibrosis in chronically infarcted hearts without triggering endogenous cardiomyocyte proliferation.
Background: Extracellular vesicles (EV) mediate the therapeutic effects of stem cells but it is unclear whether this involves cardiac regeneration mediated by endogenous cardiomyocyte proliferation. Methods: Bi-transgenic MerCreMer/ZEG (n = 15/group) and Mosaic Analysis With Double Markers (MADM; n = 6/group) mouse models underwent permanent coronary artery ligation and received, 3 weeks later, 10 billion EV (from human iPS-derived cardiovascular progenitor cells [CPC]), or saline, injected percutaneously under echo guidance in the peri-infarcted myocardium. Endogenous cardiomyocyte proliferation was tracked by EdU labeling and biphoton microscopy. Other end points, including cardiac function (echocardiography and MRI), histology and transcriptomics were blindly assessed 4-6 weeks after injections. Results: There was no proliferation of cardiomyocytes in either transgenic mouse strains. Nevertheless, EV improved cardiac function in both models. In MerCreMer/ZEG mice, LVEF increased by 18.3 ± 0.2% between baseline and the end-study time point in EV-treated hearts which contrasted with a decrease by 2.3 ± 0.2% in the PBS group; MADM mice featured a similar pattern as intra-myocardial administration of EV improved LVEF by 13.3 ± 0.16% from baseline whereas it decreased by 14.4 ± 0.16% in the control PBS-injected group. This functional improvement was confirmed by MRI and associated with a reduction in infarct size, the decreased expression of several pro-fibrotic genes and an overexpression of the anti-fibrotic miRNA 133-a1 compared to controls. Experiments with an anti-miR133-a demonstrated that the cardio-reparative effects of EV were partly abrogated. Conclusions: EV-CPC do not trigger cardiomyocyte proliferation but still improve cardiac function by other mechanisms which may include the regulation of fibrosis.
No takes yet. Share an insight, caveat, or question.
Correa et al. (2021) studied Chronically infarcted hearts (n=42). Extracellular vesicles (EV) from human iPS-derived cardiovascular progenitor cells vs. Saline (PBS) was evaluated on Endogenous cardiomyocyte proliferation and cardiac function. Extracellular vesicles did not trigger cardiomyocyte proliferation but improved LVEF by 18.3% from baseline compared to a 2.3% decrease in controls in chronically infarcted mouse hearts.
Synapse has enriched 10 related papers. Consider them for comparative context: