Co-culture pellet of human Wharton’s jelly mesenchymal stem cells and rat costal chondrocytes as a candidate for articular cartilage regeneration: in vitro and in vivo study

Abstract

Background Seeding cells are key factors in cell-based cartilage tissue regeneration. Monoculture of either chondrocyte or mesenchymal stem cells has several limitations. In recent years, co-culture strategies have provided potential solutions. In this study, directly co-cultured rat costal chondrocytes (CCs) and human Wharton’s jelly mesenchymal stem (hWJMSCs) cells were evaluated as a candidate to regenerate articular cartilage. Methods Rat CCs are directly co-cultured with hWJMSCs in a pellet model at different ratios (3:1, 1:1, 1:3) for 21 days. The monoculture pellets were used as controls. RT-qPCR, biochemical assays, histological staining and evaluations were performed to analyze the chondrogenic differentiation of each group. The 1:1 ratio co-culture pellet group together with monoculture controls were implanted into the osteochondral defects made on the femoral grooves of the rats for 4, 8, 12 weeks. Then, macroscopic and histological evaluations were performed. Results Compared to rat CCs pellet group, 3:1 and 1:1 ratio group demonstrated similar extracellular matrix production but less hypertrophy intendency. Immunochemistry staining found the consistent results. RT-PCR analysis indicated that chondrogenesis was promoted in co-cultured rat CCs, while expressions of hypertrophic genes were inhibited. However, hWJMSCs showed only slightly improved in chondrogenesis but not significantly different in hypertrophic expressions. In vivo experiments showed that all the pellets filled the defects but co-culture pellets demonstrated reduced hypertrophy, better surrounding cartilage integration and appropriate subchondral bone remodeling. Conclusion Co-culture of rat CCs and hWJMSCs demonstrated stable chondrogenic phenotype and decreased hypertrophic intendency in both vitro and vivo. These results suggest this co-culture combination as a promising candidate in articular cartilage regeneration.

Decellularized Placental Sponge: A Platform for Coculture of Mesenchymal Stem Cells/Macrophages to Assess an M2 Phenotype and Osteogenic Differentiation In Vitro and In Vivo

“…The rat critical-sized calvarial defect model has emerged as a valuable tool to investigate the effects of different biomaterials and cells on bone regeneration. In our research, we chose this model to evaluate whether our scaffold could reduce inflammation, promote macrophage polarization, and accelerate bone regeneration in the defect site. , In addition, combining biomaterial and stem cells can be a promising strategy for the renewal of injured tissues. , Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) stand out as an attractive choice due to their accessibility, resistance to aging-related damage, and robust osteogenic differentiation and proliferation capacity. , WJ-MSCs look more promising as they express low levels of HLA class I and CD40 compared to other sources of stem cells, which makes them less immunogenic and an excellent choice for clinical use, especially allogeneic stem cell therapy …”

“…94,95 Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) stand out as an attractive choice due to their accessibility, resistance to aging-related damage, and robust osteogenic differentiation and proliferation capacity. 96,97 WJ-MSCs look more promising as they express low levels of HLA class I and CD40 compared to other sources of stem cells, which makes them less immunogenic and an excellent choice for clinical use, especially allogeneic stem cell therapy. 98 Research has demonstrated that the secreted substances from bone marrow mesenchymal stem cells significantly boost the osteogenic potential of WJ-MSCs.…”

Collagen and Alginate Hydrogels Support Chondrocytes Redifferentiation In Vitro without Supplementation of Exogenous Growth Factors

“…Using pellets as controls was not considered suitable, as our primary objective was to analyze the isolated effect of hydrogels on chondrocytes without the influence of any growth factors. Maintaining pellets in culture usually requires the presence of growth factors, which could introduce confounding variables and affect the intended isolation of hydrogel effects. − Furthermore, pellets typically require a higher cell count, around 200,000 cells per pellet, which differs from the cell count used in our experiments. − Moreover, another important aspect to consider when using pellets is cell-to-cell interactions. During pellet culture, cells are compacted and in close proximity to each other.…”

Autologous Costal Chondral/Osteochondral Transplantation and Costa‐Derived Chondrocyte Implantation for Articular Cartilage Repair: Basic Science and Clinical Applications

“…This might be due to the costal cartilage taking on more of the development and maintenance of the thoracic contour, requiring more cells and regenerative potential. Some recent studies on co‐culture stem cells and costal chondrocytes also demonstrated the potential of stem cells, co‐culture, and co‐existence for cartilage regeneration and osteochondral defect repair 26,27 …”

“…Some recent studies on coculture stem cells and costal chondrocytes also demonstrated the potential of stem cells, co-culture, and co-existence for cartilage regeneration and osteochondral defect repair. 26,27 Properties of Costal Corticocancellous Bone Costal bone grafts can be harvested en bloc with reliable composition, annular cortical bone, and inner cancellous bone. 28 The corticocancellous property renders costal bone grafts two unique and inherent advantages.…”