Extracellular Vesicles From Notch Activated Cardiac Mesenchymal Stem Cells Promote Myocyte Proliferation and Neovasculogenesis

Frontiers in Cell and Developmental Biology
Wanling XuanMuhammad Ashraf

Abstract

Cardiac mesenchymal stem cells (C-MSCs) are a novel mesenchymal stem cell (MSC) subpopulation derived from cardiac tissue, which are reported to be responsible for cardiac regeneration. Notch signaling is believed to aid in cardiac repair following myocardial injury. In this study, we have investigated the role of extracellular vesicles (EVs) from Notch1 engineered C-MSCs on angiogenesis and cardiomyocyte (CM) proliferation in ischemic myocardium. C-MSCs were isolated from Notch1flox mice (C-MSCNotch1 FF). Notch1 gene deletion was accomplished by adenoviral vector-mediated Cre recombination, and Notch1 overexpression was achieved by overexpression of Notch1 intracellular domain (N1ICD). EVs were isolated by using the size exclusion column method. Proteomic composition of EV was carried out by mass spectrometry. A mouse myocardial infarction (MI) model was generated by permanent left anterior descending (LAD) coronary artery ligation. Intramyocardial transplantation of Notch1 knockout C-MSCs (C-MSCsNotch1 KO) did not have any effect on cardiac function and scar size. On the other hand, transplantation of N1ICD-overexpressing C-MSCs (C-MSCsN1ICD) showed significant improvement in cardiac function and attenuation of fibrosis as co...Continue Reading

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Citations

Jun 2, 2020·Frontiers in Bioengineering and Biotechnology·Edoardo MaghinSveva Bollini
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Armel H Nwabo KamdjeMauro Krampera
Mar 7, 2021·Nanomaterials·Laura SaludasMaría J Blanco-Prieto
Apr 20, 2021·Advanced Drug Delivery Reviews·Anika NagelkerkeMolly M Stevens

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Datasets Mentioned

BETA
PXD016578

Methods Mentioned

BETA
histone acetylation
magnetic
transmission electron microscopy
SMA
immunoprecipitation assay
transfection
coronary artery ligation

Software Mentioned

QuickGO
SequestHT
Proteome Discoverer
Graphpad Prism
ProteomeXchange
Wimasis Image Analysis Platform
ImageJ

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