Mesenchymal Stromal Cells as a Driver of Inflammaging

Abstract

Life expectancy and age-related diseases burden increased significantly over the past few decades. Age-related conditions are commonly discussed in a very limited paradigm of depleted cellular proliferation and maturation with exponential accumulation of senescent cells. However, most recent evidence showed that the majority of age-associated ailments, i.e., diabetes mellitus, cardiovascular diseases and neurodegeneration. These diseases are closely associated with tissue nonspecific inflammation triggered and controlled by mesenchymal stromal cell secretion. Mesenchymal stromal cells (MSCs) are known as the most common type of cells for therapeutic approaches in clinical practice. Side effects and complications of MSC-based treatments increased interest in the MSCs secretome as an alternative concept for validation tests in regenerative medicine. The most recent data also proposed it as an ideal tool for cell-free regenerative therapy and tissue engineering. However, senescent MSCs secretome was shown to hold the role of 'key-driver' in inflammaging. We aimed to review the immunomodulatory effects of the MSCs-secretome during cell senescence and provide eventual insight into the interpretation of its beneficial biological actions in inflammaging-associated diseases.

Keywords: MSC-secretome; SASP; immunomodulatory; pro-inflammatory cytokines.

Figure 1

SASP effects on MSCs and their microenvironment.

Figure 2

The Opposing Effects of Inflammation on the Immunomodulatory Function of hMSCs. Abbreviations: IDO, indoleamine 2,3-dioxygenase; IL, interleukin; INF, interferon; TGF, tumor growth factor; TNF, tumor necrosis factor.