An Ex-Vivo Model using Human Osteoarthritic Cartilage Demonstrates the Release of Bioactive Insulin-like growth factor- 1 from a Collagen-Glycosaminoglycan Scaffold.
Cell Biochemistry and Function
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Wardale, R., Mullen, L., Howard, D., Ghose, S., & Rushton, N. (2015). An Ex-Vivo Model using Human Osteoarthritic Cartilage Demonstrates the Release of Bioactive Insulin-like growth factor- 1 from a Collagen-Glycosaminoglycan Scaffold.. Cell Biochemistry and Function, 33 (5), 277-284. https://doi.org/10.1002/cbf.3112
Biomimetic scaffolds hold great promise for therapeutic repair of cartilage but although most scaffolds are tested with cells in vitro, there are very few ex vivo models (EVM) where adult cartilage and scaffolds are co-cultured to optimize their interaction prior to in vivo studies. This study describes a simple, non-compressive method that is applicable to mammalian or human cartilage and provides a reasonable throughput of samples. Rings of full depth articular cartilage slices were derived from human donors undergoing knee replacement for osteoarthritis (OA) and a 3mm core of a collagen/glycosaminoglycan biomimetic scaffold (Tigenix UK) inserted to create the EVM. Adult OA chondrocytes were seeded into the scaffold and cultures maintained for up to 30 days. EVM were stable throughout experiments and cells remained viable. Chondrocytes seeded into the EVM attached throughout the scaffold and in contact with the cartilage explants. Cell migration and deposition of ECM proteins in the scaffold was enhanced by growth factors particularly if the scaffold was preloaded with growth factors. This study demonstrates that the EVM represents a suitable model which has potential for a testing a range of therapeutic parameters such as numbers/types of cell, growth factors or therapeutic drugs before progressing to costly pre-clinical trials. Significance Pre clinical trials of biomaterials for cartilage repair are very costly and all too often studies progress directly from in vitro studies using isolated cells to in vivo studies without investigating the interaction between the target tissue and the scaffold. Our study uses viable cartilage from adult human donors with osteoarthritis and therefore represents the exact scenario that the scaffold is designed for. The system is cheap and simple to set up and is suitable for a 48 well plate format meaning a reasonable throughput is obtainable. This lends the model to therapeutic drug testing.
Regenerative medicine, cartilage, osteoarthritis, scaffold
The authors would like to kindly acknowledge funding from the EPSRC and Tigenix Ltd (LM), Technology Strategy Board and Tigenix Ltd (JW) and the NIHR (DH).
External DOI: https://doi.org/10.1002/cbf.3112
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248101
Attribution 4.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/4.0/uk/