Dynamics of Matrix Metalloproteinase Activity and Extracellular Matrix Proteins Content in the Process of Replicative Senescence of Human Mesenchymal Stem Cells

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.