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obtained after 5 weeks. (Data not shown) These results demonstrate that h BMSCs have an additional effect on chondrocytes in mixed-cell-type populations in vitro , in particular in combination with b NCs. Figure 2. Cartilage matrix formation in constructs containing h BMSCs and/or chondrocytes, 3 weeks after in-vitro culture. Biochemical evaluation of the sGAG (A) and collagen (B) content, 3 weeks after culture in alginate. The left graphs demonstrate the amount of matrix components per construct, whereas for the right graphs matrix production is normalized to the initial number of seeded PCs. A control condition - containing similar amounts of chondrocytes (0.8 million/ml) without supplementation of h BMSCs - was evaluated to determine the additional effect of h BMSCs (3.2 million/ml) on chondrocytes in co-cultures (white line). *, ** or *** indicates p -values smaller than 0.05, 0.01 or 0.001 respectively compared to the control condition. Data are shown as mean ± SD. For statistical evaluation, a mixed model was used followed by a Fisher’s least significant post-hoc comparisons test . PC = Primary Chondrocyte ; h BMSC = human Bone-marrow-derived Mesenchymal Stem Cell ( n=3 experiments with 3 different donors) ; b EC = bovine Ear Chondrocyte ( n=3 experiments with 3 pools of donors) ; b NC = bovine Nasal Chondrocyte ( n=3 experiments with 3 pools of donors). Per experiment, 3 samples were used for analyses. 116 CHAPTER 6

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