Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair : Superiority of embryonic stem cells

• Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi och kardiovaskulära sjukdomar (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiology and Cardiovascular Disease (hsv//eng)

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

angiogenesis

fibrosis

immunomodulation

myocardial ischaemia-reperfusion injury

regeneration

small extracellular vesicles

adverse outcome

antifibrotic activity

Article

BMSC cell line

cardiac muscle cell

cardiac stem cell

cell function

cell therapy

clinical effectiveness

controlled study

down regulation

exosome

fibroblast

heart surgery

human

human cell

human embryonic stem cell

immortalized cell line

in vitro study

in vivo study

myocardial ischemia reperfusion injury

outcome assessment

protein content

proteomics

RNA analysis

transcriptomics

Bioinformatik

Bioinformatics

angiogenesis

fibrosis

immunomodulation

myocardial ischaemia-reperfusion injury

regeneration

small extracellular vesicles

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)