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• W2327594880 abstract "Purpose: Several in vivo models have been developed to validate and analyze biomaterials for the treatment of damaged cartilage. Preclinical models are well represented by large animals, especially ovine and swine models. However, in such models there is a genetic heterogeneity and a need of high number of animals to reach statistical power. In addition, their housing and maintenance is extremely expensive. Murine and laprine animal models are powerful alternatives to bypass these limitations, but reduced size and spontaneous cartilage healing limit their use. The aim of this work was to develop an ectopic screening in vivo model that would provide a tool to validate different materials or cell treatments before large animals studies. This ectopic model should provide a chondrogenic environment to analyze in a simpler and faster way the typical processes that developed in a normal or injured joint. Methods: Osteochondral biopsies were harvested from swine knee joints of 6 mm diameter wide and 4 mm high (N=10). The samples received a four mm diameter full chondral injury without disturbing the subchondral bone. Osteochondral plugs (OC) were implanted subcutaneously into seven weeks old immunodeficient Rag2 mice (Balb/cA Rag2-/- γC-/-), three OC plugs per animal. Five groups were created, n=2 per group: Group 1, OC plugs receiving fibrin implants; Group 2, OC plugs receiving chondrocytes embedded in fibrin, Group 3, plugs receiving human chondrocytes embedded in fibrin plus 60 ng of TGFβ; Group 4, OC plugs receiving a mix of human bone marrow mesenchymal stem cells (BMSCs) and human chondrocytes (80:20) embedded in fibrin and; Group 5, OC plugs receiving a mix of BMSCs and chondrocytes (80:20) in fibrin plus 60 ng of TGFβ. Human chondrocytes were isolated from healthy areas of femoral condyles of OA patients receiving a total knee replacement. BMSCs were isolated from bone marrow aspirates from OA patients. Animals were housed after the surgery for 6 weeks. Later, implants were evaluated by histology and immunohistochemistry. Results: All the implanted OC plugs showed neo-vascularization and maintained their chondral and bone vitality after 6 weeks of implantation. Active remodeling of the subchondral bone in close contact with cartilage was detected, although not on the distant part of the plugs. The articular cartilage of the Group 1 did not show any spontaneous repair. Comparing the different cell-based treatments, the best histological and immunohistological results were obtained in Group 3 with detection of GAG and type II collagen neo-synthesis in the implant zone (Figure 1). Conclusions: With this proof of concept we validated a feasible in vivo model to evaluate new cell therapies and biomaterials. With this innovative ectopic implantation model, it is possible to assess biomaterials and cells in an osteochondral environment minimizing the use of expensive and valuable large animals. Acknowledgments: This work was supported by HydroZONES funded by the European Commission within the 7th Framework Programme under Grant Agreement nº 309962" @default.
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• W2327594880 date "2016-04-01" @default.
• W2327594880 modified "2023-09-30" @default.
• W2327594880 title "Could an in vivo ectopic model help us to evaluate the regeneration process in an injured joint?" @default.
• W2327594880 doi "https://doi.org/10.1016/j.joca.2016.01.319" @default.
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