Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient’s life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.

Recently, skeletal stem cells were shown to be present in the epiphyseal growth plate (epiphyseal skeletal stem cells, epSSCs), but their function in connection with linear bone growth remains unknown. Here, we explore the possibility that modulating the number of epSSCs can correct differences in leg length. First, we examined regulation of the number and activity of epSSCs by Hedgehog (Hh) signaling. Both systemic activation of Hh pathway with Smoothened agonist (SAG) and genetic activation of Hh pathway by Patched1 ( Ptch1 ) ablation in Pthrp-creER Ptch1 ^fl/fl tdTomato mice promoted proliferation of epSSCs and clonal enlargement. Transient intra-articular administration of SAG also elevated the number of epSSCs. When SAG-containing beads were implanted into the femoral secondary ossification center of 1 leg of rats, this leg was significantly longer 1 month later than the contralateral leg implanted with vehicle-containing beads, an effect that was even more pronounced 2 and 6 months after implantation. We conclude that Hh signaling activates growth plate epSSCs, which effectively leads to increased longitudinal growth of bones. This opens therapeutic possibilities for the treatment of differences in leg length.

Ear reconstruction surgeries for congenital deformities and trauma are common, highlighting the need for improved cartilage regeneration. Lactoferrin (LF), a natural and cost-effective protein, is promising due to its anti-inflammatory, antimicrobial, and prochondrogenic properties. This study investigates the effects of LF on the viability, proliferation, and chondrogenesis of rabbit auricular chondrocytes. For in vitro studies, auricular chondrocytes were cultured for three passages, after which 3D pellets were formed. LF significantly increased chondrocyte metabolic activity by 1.5 times at doses of 10 and 500 μg/mL. At passage 3, LF at concentrations of 10 and 100 μg/mL increased cell proliferation rates by 2- and 1.5-fold, respectively. Immunohistochemical staining of the pellets demonstrated that LF at 10 μg/mL increased the amount of sex-determining region Y-Box Transcription Factor 9 (Sox9)+ cells by 30%, while at 100 μg/mL, it doubled the type II collagen deposits. For in vivo studies, a rabbit ear defect model was utilized. On post-operative day 60, the LF-treated group exhibited more mature cartilage regeneration, with a higher density of elastic fibers. By day 90 post-surgery, LF application led to the restoration of normal elastic cartilage throughout the defect. These findings suggest that LF promotes auricular chondrocytes chondrogenesis and could be beneficial for tissue engineering of the elastic cartilage.

Mast cells are best known for their involvement in the pathogenesis of allergic reactions and inflammation. Due to the wide variety of activation methods and the various mediators that mast cells can synthesize and store, they can regulate all stages of the inflammatory process. There are a large amount of data describing the role of mast cells in the development of autoimmune rheumatoid arthritis, but their role in the development of inflammatory traumatic osteoarthritis remains poorly described. However, non-autoimmune cartilage damage is the main reason for joint replacement surgeries. As important regulators of the inflammatory process, mast cells could be an interesting target for the treatment of osteoarthritis. Herein, we summarize the knowledge about the role of mast cells in the pathogenesis of osteoarthritis and outline various approaches that, to varying degrees, seem promising for the correction of the disease.