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doublings instead of culture passages might have been more appropriate, since population doublings more accurately reflect cell growth and thus cell aging. However, since nasal chondrocytes had most doublings in four passages but still produced most cartilage, a direct link between doublings and cartilage formation seems unlikely. How all the parameters such as number of doublings, expansion speed, initial seeding density, growth factors present in the medium or produced by the cells themselves exactly determine dedifferentiation and possible loss of chondrogenic capacity during monolayer expansion remains to be elucidated. Finally, we have demonstrated large donor variation in constructs containing ACs or BMSCs. Nevertheless these differences were not based on a donor-age effect nor explained by the use of healthy versus diseased ACs. Moreover, donors for nasal cartilage appeared younger than other sources. Although there is a possibility that the donor-age has influenced the general outcome of our study, improved chondrogenic and proliferative capacity of nasal chondrocytes was also stated by others in literature. [39, 48, 52] In summary, we have demonstrated that cartilage matrix formation and functionality are cell source dependent. ACs possess the highest chondrogenic capacity in vitro , while ECs and NCs are most potent for cartilage regeneration after subcutaneous implantation, making ECs and NCs attractive cell sources for future cell-based cartilage repair. Only for constructs containing nasal chondrocytes, sGAG and collagen content were associated with biomechanical functionality of the constructs, indicating the differences in matrix component assembly by different cell sources. The inability of ACs to increase cartilage matrix in vivo may be due to a loss of chondrogenic capacity in the absence of mechanical loading or growth factor stimulation. Although MSCs are considered as a promising cell sources for the reconstruction of cartilage defects, it appears that improvements in cell culture conditions for both BMSCs and AMSCs are needed. Acknowledgment The authors thank the Departments of Orthopaedic Surgery, Plastic and Reconstructive Surgery, and Otorhinolaryngology at Erasmus MC for their assistance in obtaining ear, nasal and articular cartilage as well as bone marrow and adipose tissue, and CellMed (Alzenau, Germany) for providing the clinical grade alginate. The study was performed within the framework of EuroNanoMed (EAREG-406340-131009/1) and funded by SenterNovem (ENM09001). 81 CARTILAGE-FORMING CAPACITY OF SEVERAL CELL SOURCES 4