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

BMB Reports 2020년 53권 2호 p.118 ~ 123
강인숙 ( Kang In-Sook ) - Ewha Womans University School of Medicine Department of Internal Medicine

서주원 ( Suh Joo-Won ) - Ewha Womans University College of Natural Sciences Department of Life Science
이미니 ( Lee Mi-Ni ) - Ewha Womans University College of Natural Sciences Department of Life Science
이채영 ( Lee Chae-Young ) - Ewha Womans University College of Natural Sciences Department of Life Science
 ( Jin Jing ) - Ewha Womans University College of Natural Sciences Department of Life Science
 ( Lee Chang-Jin ) - Rosetta Exosome Inc.
양영일 ( Yang Young-Il ) - Inje University Paik Institute for Clinical Research
장양수 ( Jang Yang-Soo ) - Yonsei University College of Medicine Severance Cardiovascular Hospital Division of Cardiology
오구택 ( Oh Goo-Taeg ) - Ewha Womans University College of Natural Sciences Department of Life Science

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 CD90low, c-kitnegative, CD105positive 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 CD90lowc-kitnegativeCD105positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair.

키워드

Cardiovascular disease; Extracellular vesicles; Mesenchymal stem cell; Regeneration
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