Characterization of Human Cardiac Mesenchymal Stromal Cells and Their Extracellular Vesicles Comparing With Human Bone Marrow Derived Mesenchymal Stem Cells

Abstract

Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90 low , c-kit negative , CD105 positive phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90 low c-kit negative CD105 positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair. [BMB Reports 2020; 53(2): 118-123]

MicroRNA Profiling of HL-1 Cardiac Cells-Derived Extracellular Vesicles

“…Kang I. S. et al performed a characterization of the EVs isolated from human cardiac mesenchymal stromal cells and compared them with those isolated from human bone marrow-derived mesenchymal stem cells. The in vitro results of this study demonstrated that EVs derived from human cardiac mesenchymal stromal cells exhibited a potent angiogenic effect compared to EVs derived from bone marrow mesenchymal stem cells [ 74 ]. Moreover, Leitolis A. demonstrated that EVs isolated from the human heart induced proliferation and angiogenesis in endothelial cells, promoting wound healing, and reducing the adhesion of mesenchymal stem cells.…”

Tissue Regeneration Capacity of Extracellular Vesicles Isolated From Bone Marrow-Derived and Adipose-Derived Mesenchymal Stromal/Stem Cells

“…ADMSC-derived EVs enhanced angiogenic tube formation in human brain microvessel endothelial cells via increased expression of miR-181b-5p, which, in turn, directly targeted expression of the ion channel protein TRPM7 (Yang et al, 2018). Similarly, BMMSC-derived EVs induced angiogenic tube formation in HUVECs (Teng et al, 2015;Xie et al, 2017;Kang et al, 2020;Yu M. et al, 2020;Zhang et al, 2020) and enhanced expression of the angiogenesisrelated genes VEGF, ANG1, and ANG2 in hBMMSCs (Takeuchi et al, 2019) and the mRNA expression of PDGF, EGF, and ANG1 in HUVECs (Yu M. et al, 2020). In a rare study that directly compared EVs derived from the three most commonly employed clinical MSC sources, i.e., BMMSCs, ADMSCs and UCMSCs, ADMSC-derived EVs yielded the highest in vitro protein expression levels of VEGF, bFGF, and HGF in rat neonatal cardiomyocytes and also showed the strongest inhibitory effect on apoptosis (Xu H. et al, 2020).…”

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

“…However, only few studies compared EVs from MSCs isolated from different sources. It has been recently reported that EVs from adipose tissue-derived MSCs (AD-MSCs) and from cardiac MSCs exhibit more potent angiogenic capacities than bone marrow-derived MSCs (BM-MSCs) (Chance et al, 2020;Kang et al, 2020). In addition, the capacity of EV production and secretory profile are higher in BM-MSCs than AD-MSCs, supporting a differential activity of EVs from different MSCs (Villatoro et al, 2019).…”