Osteoarthritis (OA) is one of the most common progressive musculoskeletal diseases affecting synovial joints. Cell therapies and tissue engineering approaches based on mesenchymal stem/stromal cells (MSCs) are increasingly studied in the therapy of degenerative articular cartilage and bone diseases. MSCs are a heterogeneous group of plastic-adherent, fibroblast-like cells that can self-renew or differentiate into bone, adipose, or cartilage tissue in vitro. After birth, MSCs are maintained in many tissues. They self-renew in niches, and when given a suitable signal, they become activate, differentiate into a specific cell line, migrate to the site of damaged tissue, and regenerate it. In addition, MSCs mediate anti-inflammatory and immunomodulatory effects. The goal of therapies using MSCs is to activate endogenous repair mechanisms and establish functional regeneration of damaged tissues. MSCs actively participate in all stages of healing after tissue damage, and recent studies also demonstrate that MSCs are involved in the pathophysiology of OA itself. To be able to develop new treatment options for the osteoarthritis of large joints, it is important to understand the importance of MSCs in the regeneration of affected tissues and to precisely define the role of MSCs in the development of OA.
The purpose of our research was to determine the differences in the ability of MSCs to form hyaline cartilage in patients without and with early degenerative changes of the hip. We included 11 subjects and collected their tissue samples during arthroscopy at the Orthopedic Clinic in Ljubljana. Three samples of synovium from different anatomical sites of the hip and a sample of trabecular bone were collected from the subjects. Primary MSCs were isolated from tissue samples and differentiated into chondrocytes in vitro. Samples for histology were prepared from the chondrogenic pellets. The presence of collagen type II was evaluated on paraffin slides using the direct immunofluorescence method. First, we compared the ability of MSCs to form hyaline cartilage in vitro in patients without OA and those with early OA. The results of our research showed no statistically significant differences between the groups. However, we found that the proportion of collagen type II positive pellets was lower in the OA group. This suggests that the cells of OA patients have lower ability to form collagen type II, hence lower regeneration propensity for cartilage regeneration. We also did not demonstrate statistically significant differences in chondrogenic potential between MSCs obtained from synovium or bones both in the group of patients without OA and in the group of early OA patients. In the group of OA patients, we assessed a higher proportion of collagen type II negative pellets formed by synovial MSCs. The latter could indicate that synovial cells are more exposed to the unfavourable inflammatory environment in the joint and are therefore depleted earlier than bone derived MSCs. In the group of patients without OA, we assessed a higher proportion of positive samples in the synovial MSC group. From this, it could be concluded that synovial MSCs have a better regenerative potential for cartilage repair in patients without OA. The research raises questions regarding the differences in the chondrogenic ability of MSCs between patients with early or late OA, and differences in the involvement or depletion of MSCs from various tissues of the affected joint. We suggest that the answers to the questions raised should be found through further studies, as this would additionally explain the pathophysiology of OA and help in the development of new treatment methods for degenerative joint diseases.
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