Dynamics of Matrix Metalloproteinase Activity and Extracellular Matrix Proteins Content in the Process of Replicative Se
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mics of Matrix Metalloproteinase Activity and Extracellular Matrix Proteins Content in the Process of Replicative Senescence of Human Mesenchymal Stem Cells I. V. Voronkinaa, b, *, L. V. Smaginaa, N. B. Bildyuga, A. S. Musorinaa, and G. G. Poljanskayaa aInstitute
of Cytology Russian Academy of Sciences, St. Petersburg, 194064 Russia Institute of Experimental Medicine, St. Petersburg, 197376 Russia *e-mail: [email protected]
b
Received November 11, 2019; revised December 9, 2019; accepted December 13, 2019
Abstract—A comparative analysis of mesenchymal stem cells (MSCs) of differing origin is important because of their specific interaction with a unique microenvironment (niche) in a particular tissue. Some cellular processes are regulated through the interaction of extracellular matrix (ECM) proteins with matrix metalloproteinases (MMPs). In this work, we compared the dynamics of MMP activity and the level of ECM proteins during replicative senescence of three lines of human MSCs obtained from Wharton’s jelly of human umbilical cord (MSCWJ-1 line), eyelid skin (DF-2 line), and human epicardial adipose tissue isolated during coronary artery bypass grafting (ADH-MSC line). The fractions of cells with β-galactosidase enzyme activity (marker of replicative senescence) and the content of ECM proteins (fibronectin and type I collagen), as well as the activity of MMP-1, MMP-2, and MMP-9, were analyzed during long-term cultivation. It was found that three lines differ in the content of fibronectin, type 1 collagen, and MMP activity during the replicative senescence. Cells of the ADH-MSC line are mostly different from the other two lines in terms of aging rate, ECM protein content, and MMP activity. The reason for this discrepancy is that the cells are obtained from the tissue of a patient having heart disease. Keywords: mesenchymal stem cells, senescence, extracellular matrix, matrix metalloproteinases DOI: 10.1134/S1990519X20050107
INTRODUCTION The importance of the characteristics of mesenchymal stem cells (MSCs) follows from their specific interaction with a unique microenvironment (niche) typical for a tissue. Intercellular interactions and various bioactive molecules regulate proliferation, survival, migration, aging, differentiation potential, and other cell properties. Given the unique microenvironment of cells in certain tissues of the human body, it is of considerable interest to conduct a comparative analysis of the characteristics that are crucial in maintaining the status of MSCs in accordance with the requirements of the International Society of Cell Therapy (Dominici et al., 2006; Sensebé et al., 2010), as well as a number of other properties responsible for the most important cellular processes. To date, a great deal of data have been accumulated on a comparative analysis of human MSCs isolated from different human adult and embryonic tissues and from extra-embryonic organs, as well as embryonic stem cells (Fong et al., 2007; Abbreviations: ECM—extracellular matrix, MMP—matrix metalloproteinase, MSC—mesen
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