MESENCHYMAL STEM CELLS AND FIBROBLASTS IN AGE-RELATED REMODELING OF THE MUSCULOSKELETAL SYSTEM

Mesenchymal stem/stromal cells (MSCs) and fibroblasts are present in normal tissues to maintain tissue homeostasis and share a number of common features such as spindle-shaped morphology, localization in connective tissue, and multipotency. During inflammation, fibroblasts and MSCs non-specifically respond to injury via two mechanisms of action: immunomodulation and regeneration. Upon tissue injury, MSCs are activated, proliferate, and differentiate. With age and, in particular, in degenerative diseases of the musculoskeletal system (diseases of the muscles, joints and bones), the regenerative capacity of MSCs is lost or redirected to the production of other non-functional cell types such as adipocytes and fibroblasts, which provide much of the structural framework of almost all tissue types. By performing an immunosuppressive role, MSCs and fibroblasts contribute to the normal resolution of inflammation, which is a prerequisite for successful tissue repair. The aim of the review is to provide an understanding of the common and opposite properties of MSCs and FB from the standpoint of age-related changes in the musculoskeletal system in order to develop approaches to their complementary assistance for successful tissue regeneration. The key features of aging MSC and fibroblast are presented, and it is indicated that additional studies are needed on the cellular mechanisms that together generate dysfunctions of individual niches of terminal differentiated cells during aging. The currently existing technologies of cell therapy for the musculoskeletal system diseases involving MSCs and fibroblasts are presented.