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.

Screening and identification of hub genes of scar physique via weighted gene co-expression network analysis

“…[14] Related studies have shown that mesenchymal stromal cells as drivers of inflammation. [15] The cell senescence in the skin microenvironment is related to inflammation. With the occurrence of aging, the body's ability to resolve inflammation is significantly reduced, leading to an imbalance between pro-inflammatory and anti-inflammatory.…”

Senescent Markers Expressed by Periodontal Ligament-Derived Stem Cells (PDLSCs) Harvested from Patients with Periodontitis Can Be Rejuvenated by RG108

“…Interestingly, CD73 and CD90 were always higher than 95%, but CD105 was overall less expressed and more susceptible to the cell milieu (healthy vs. inflamed). Recently, the role of CD105 in MSCs has gained attention owing to its possible association with immunomodulatory functions [ 25 ], besides the differences depending on cell culture conditions and passages [ 26 ]. CD105-MSCs have a significant inhibitory effect on the expression of lymphocytes in comparison with CD105+ cells [ 27 ].…”

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals

“…Further, MSCs secretome releases several neurotrophic factors, which are all linked to axo-glial regeneration, such as neurotrophin-1 (NT-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT4), ciliary-derived neurotrophic factor (CDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (bFGF), and ciliary neurotrophic factor (CNTF) [69]. However, recent studies show that cellular aging (i.e., donor age, increased passages, replication stress, telomere deletion, and cellular exhaustion) drives MSCs into senescence phenotype [70,71]. Resulting senescent MSCs are known to exhibit pro-inflammatory effects and impede tissue regeneration [70][71][72].…”

“…However, recent studies show that cellular aging (i.e., donor age, increased passages, replication stress, telomere deletion, and cellular exhaustion) drives MSCs into senescence phenotype [70,71]. Resulting senescent MSCs are known to exhibit pro-inflammatory effects and impede tissue regeneration [70][71][72].…”