Hybrid pig versus Göttingen minipig-derived cartilage and chondrocytes show pig line-dependent differences

Abstract

Minipigs are widely used as a large animal model for cartilage repair. However, many in vitro studies are based on porcine chondrocytes derived from abundantly available premature hybrid pigs. It remains unclear whether pig line-dependent differences exist which could limit the comparability between in vitro and in vivo results using either hybrid or miniature pig articular chondrocytes. Porcine knee joint femoral cartilage was isolated from 3- to 5-month-old hybrid pigs and Göttingen minipigs. Cartilage from both pig lines was analysed for thickness, zonality, cell content, size and proteoglycan deposition. Cultured articular chondrocytes from both pig lines were investigated for gene and/or protein expression of cartilage-specific proteins such as type II collagen, aggrecan, the chondrogenic transcription factor Sox9, non-specific type I collagen and the cell-matrix receptor β1-integrin. Cartilage was significantly thinner in the miniature pig compared to the hybrid pig, but the differences between the medial and lateral femur condyles did not reach a significant level. Knee joint cartilage zone formation started only in the minipig, whereas cellularity and cell diameters were comparable in both pig lines. Blood vessels could be detected in the hybrid pig but not the minipig cartilage. Sulphated proteoglycan deposition was more pronounced in cartilage zones II-IV of both pig lines. Minipig chondrocytes expressed type II and I collagen, Sox9 and β1-integrin at a higher level than hybrid pig chondrocytes. These distinct line-dependent differences should be considered when using hybrid pig-derived chondrocytes for tissue engineering and Göttingen minipigs as a large animal model.

Macroscopical, Histological, and In Vitro Characterization of Nonosteoarthritic Versus Osteoarthritic Hip Joint Cartilage

“…Experiments with human-derived chondrocytes are superior to using animalderived samples due to interspecies differences. 37,38 Therefore, the facts reported here for FNF-versus OA-derived chondrocytes, which are the main chondrocyte sources of human origin for research, help to assess their peculiarities and its potential influence on experiments. With regard to further characterize the extent of complement activation during OA progression, other complement factors such as C3, C4, and C5 and the split fragments such as C3a and C5a should also be included in future studies.…”