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An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

  • Bartz, Christoph1
  • Meixner, Miriam1
  • Giesemann, Petra1
  • Roël, Giulietta1
  • Bulwin, Grit-Carsta1
  • Smink, Jeske J.1
  • 1 co.don® AG, Biotechnology and Tissue Engineering, Teltow, Germany , Teltow (Germany)
Published Article
Journal of Translational Medicine
Springer (Biomed Central Ltd.)
Publication Date
Nov 15, 2016
DOI: 10.1186/s12967-016-1065-8
Springer Nature


BackgroundCell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don’s chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany.MethodsChondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation.ResultsAfter the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential after implantation, reflected by more newly formed repair tissue.ConclusionThis demonstrated that aggrecan protein expression levels in spheroids before implantation can potentially be used as surrogate potency assay for the cartilage cell transplant to predict its regenerative capacity after implantation in human patients.

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