Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Their Features and Impact on Fibrosis and Myogenesis in Vitro
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esenchymal Stromal Cell-Derived Extracellular Vesicles: Their Features and Impact on Fibrosis and Myogenesis in Vitro1 A. N. Novokreshchenovaa, *, N. N. Butorinaa, O. V. Payushinab, O. N. Shevelevaa, E. G. Evtushenkoc, and E. I. Domaratskayaa aKoltzov
Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, Moscow, 119991 Russia cLomonosov Moscow State University, Chemistry Department, Moscow, 119991 Russia *e-mail: [email protected]
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Received February 25, 2020; revised May 7, 2020; accepted May 7, 2020
Abstract—Extracellular vesicles (EVs) and, particularly, exosomes are becoming a promising material for “cell-free therapy” of many pathologic conditions. In the recent years therapeutic effects of mesenchymal stromal cells (MSCs) have been attributed to their secretory factors, including EVs. In this study we aim to investigate how EVs produced by MSCs of different tissue origin can influence myogenesis and fibrosis–the main processes that accompany skeletal muscle regeneration. Bone marrow, adipose tissue, intact muscle, and injured muscle-derived rat MSCs were obtained and cultured according to standard protocols. EVs were obtained by ultracentrifugation from the MSC-conditioned medium of cell passages 2 and 3. The effects of EVs were estimated on the in vitro models of myogenesis and fibrosis. Samples of isolated EVs contained nano-sized vesicles that carried some exosomal markers. Promyogenic microRNA were found in EVs from bone marrow and muscle MSCs. We found that MSC-derived EVs from all sources significantly increased the number of newly formed myotubes in myoblast culture in vitro and also reduced the number and size of fibrotic nodules in muscle fibroblast culture in vitro. Our results suggest that MSC-derived EVs indeed possess antifibrotic and promyogenic potentials. However, the role of microRNA in these processes is yet to be determined, and the effect of EVs on skeletal muscle regeneration is yet to be tested in vivo. Keywords: skeletal muscle, regeneration, mesenchymal stromal cells, extracellular vesicles, biomedicine DOI: 10.1134/S1990747820100013
INTRODUCTION In the recent years it has been widely accepted that mesenchymal stromal cells (MSCs) conditioned medium and extracellular vesicles (EVs) on their own possess the regenerative potential, previously attributed only to MSCs, due to a number of transported proteins, lipids and nucleic acids. Development of methods of EV application for disease treatment is seen as a transition from cell therapy to “cellfree therapy”, which has a number of advantages. The general hazard of stem cell injection and teratoma formation is eliminated, as well as the question of uncertainty of MSCs survival and sufficient activity after transplantation. Apart from that, EVs are easier to manipulate and can be stored for a while, which makes 1 The article is published in the original.
Abbreviations: AT, adipose tissu
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