1. Introduction
deaths
ISCHEMIC HEART DISEASE, ISCHEMIC HEART DISEASE, CARDIAC DISEASE
Small extracellular vesicles (EVs) and their cargo are an important component of cell-to-cell communication in cardiac disease. Allogeneic adipose derived stem cells (ADSCs) are thought to be a potential approach for cardiac regenerative therapy in ischemic heart disease. The SCIENCE study investigated the effect of ADSCs administered via intramyocardial injection on cardiac function in patients with ischemic heart disease. The aim of this substudy, based on samples from 15 patients, was to explore small EV miRNA dynamics after treatment with ADSCs compared to a placebo. Small EVs were isolated at several timepoints after the percutaneous intramyocardial application of ADSCs. No significant effect of ADSC treatment on small EV concentration was detected. After 12 months, the expression of miR-126 decreased significantly in ADSC patients, but not in the placebo-treated group. However, all cardiac miRNAs correlated with plasma cardiac biomarkers. In line with the overall negative results of the SCIENCE study, with the exception of one miR, we did not detect any significant regulation of small EV miRNAs in this patient collective.Ischemic heart disease resulted in 17.9 million deaths worldwide in 2019, despite improvements in diagnosis and treatment within recent years. (WHO, 2021) The current treatment approaches comprise pharmaceutical and surgical therapies, which alleviate symptoms and impede revers remodeling [Extracellular vesicles (EVs) are small membrane-enclosed vesicles originating from various cell types. They are found in biological fluids such as blood, urine, and cerebrospinal fluid. In recent years, they have been studied extensively, and their role in cell-to-cell communication is of special interest [Mature microRNAs (miRNAs) are small non-coding RNAs with a length of 18–25 nucleotides that regulate protein expression by pairing with the 3′ untranslated region (UTR) of target messenger RNAs (mRNA), resulting in either mRNA cleavage or repression of translation [In contrast with small and large animal studies, human cardiac stem cell treatments have comparatively disappointing results [The SCIENCE study was a multicenter, randomized, double-blinded, placebo-controlled study that was conducted in six European centers (The aim of our SCIENCE substudy was to investigate the effect of allogeneic ADSC treatment on small EVs isolated from peripheral blood, and small EV miRNA expression of selected miRNAs in this setting, in order to detect possible changes in the landscape of small EVs induced by percutaneous intramyocardial application of allogeneic ADSCs. 