title: Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage.
abstract: Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC) therapy are gaining acceptance for knee-osteoarthritis (OA) treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL). At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.
authors.affiliation: Department of Chemistry & Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia; Translational Regenerative Medicine Research Laboratory, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Succar
authors.affiliation: Regeneus Ltd., 25 Bridge Street, Pymble, NSW 2073, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Medynskyj
authors.affiliation: Australian Proteome Analysis Facility, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Breen
authors.affiliation: Translational Regenerative Medicine Research Laboratory, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Quirindi Vet Clinic, 81 Pryor Street, Quirindi, NSW 2343, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Batterham
authors.affiliation: Department of Chemistry & Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia; Australian Proteome Analysis Facility, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Molloy
authors.affiliation: Translational Regenerative Medicine Research Laboratory, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Regeneus Ltd., 25 Bridge Street, Pymble, NSW 2073, Australia.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Herbert