DIFFERENTIATION POTENTIAL OF THE MESENCHYMAL STROMAL CELLS DURING REPLICATIVE SENESCENCE

Abstract

Mesenchymal stromal/stem cells (MSCs) are capable of multilinear differentiation and participate in tissue homeostasis including the remodeling and reparation processes. With aging these cells more and more often activatesenescence (cell aging) that alters cell functions and microenvironment which can be the reason for age-related pathologies. One of the features of senescent MSCs is thought to be a decline of multipotency that may limit their reparative functions in tissues. The paper presents a study of the MSCs osteogenic and adipogenic potential during replicative senescence. A decline of the MSCs adipogenic potential was associated with downregulation of PPARG,(a key transcription regulator of adipogenesis). There was evidence of reciprocal increasing of the osteogenic potential even though the several positive osteogenesis regulators (BMP2, BMP6, IGF1, IL1B) were downregulated. Besides, during differentiation matrix calcification was enhanced and osteoprotegerin concentration increased that can be an issue in context of atherosclerotic plaques calcification in elder people. Expression of key osteogenesis regulator RUNX2 and markers SPARC, SPP1, COL1A1, BGLAP remained stable during replicative senescence of MSCs.