Abstract
Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs’ biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs’ characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications.
Highlights
Many joint disorders, such as osteoarthritis, can lead to cartilage defects
To demonstrate an age-related ability of SfMSCs to differentiate toward chondrogenic phenotypes, the expression of mRNA chondrogenic markers and the deposition of proteoglycans were analyzed after 21 days of in vitro stimulation with chondrogenic factors
Results showed a reduction in BrdU incorporation, during the S-phase of the cell cycle, in SfMSCs isolated in equine donors of 12 years old (12Y), 23 years old (23Y), and 40 years old (40Y) groups compared to young donors (3Y) (Figure 3)
Summary
Cells 2019, 8, 1116 stromal cells (MSCs). For this reason, articular cartilage defects remain a real challenge in the field of regenerative medicine [1]. A great deal of effort has been made regarding cell therapy based on the use of MSCs, often in combination with biomaterials, in order to improve tissue regeneration. MSCs still represent a good candidate for tissue repair and regeneration [2,3]. MSCs or mesenchymal progenitor cells can be defined as non-hematopoietic, self-renewing cells that can be expanded ex vivo and induced to terminally differentiate, under certain conditions, into cells of mesenchymal lineage, including osteoblasts [4,5], chondrocytes [6,7,8], adipocytes [9], and hematopoietic-supporting stroma [10]
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