Royal College of Surgeons in Ireland
Time-dependent anabolic response of hMSC-derived cartilage grafts to hydrostatic pressure.pdf (2.13 MB)

Time-dependent anabolic response of hMSC-derived cartilage grafts to hydrostatic pressure

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journal contribution
posted on 2023-10-06, 16:14 authored by Farhad Chariyev-Prinz, Nuno Neto, Michael G Monaghan, Daniel KellyDaniel Kelly

It is generally accepted that the application of hydrostatic pressure (HP) is beneficial for MSC chondrogenesis. There is, however, evidence to suggest that the timing of application might determine its impact on cell fate and tissue development. Furthermore, understanding how the maturity of engineered cartilage affects its response to the application of HP can provide critical insight into determining when such a graft is ready for in vivo implantation into a mechanically loaded environment. In this study, we systematically examined chondrogenic maturation of hMSCs over 35 days in the presence of TGF-β3 in vitro. At specific timepoints, the response of hMSCs to the application of HP following the removal of TGF-β3 was assessed; this partially models conditions such grafts will experience in vivo upon implantation. In free swelling culture, the expression of chondrogenic (COL2A1 and ACAN) and hypertrophic (COL10A1) markers increased with time. At early timepoints, the expression of such markers continued to increase following TGF-β3 withdrawal; however, this was not observed after prolonged periods of chondrogenic priming (35 days). Interestingly, the application of HP was only beneficial after 35 days of chondrogenic priming, where it enhanced sGAG synthesis and improved key chondrogenic gene ratios. It was also found that HP can facilitate a metabolic shift towards oxidative phosphorylation, which can be viewed as a hallmark of successfully differentiating MSCs. These results point to the importance of mechanical loading as a key stimulus for maintaining a chondrogenic phenotype once MSCs are removed from chemically defined culture conditions. 


European Union’s Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 721432

Trinity College Dublin, Provost’s PhD Award

SFI Infrastructure Programme: Category D Opportunistic Funds Call (16/RI/3403)



The original article is available at

Published Citation

Chariyev-Prinz F, Neto N, Monaghan MG, Kelly DJ. Time-dependent anabolic response of hMSC-derived cartilage grafts to hydrostatic pressure. J Tissue Eng Regen Med. 2023; 9976121

Publication Date

23 August 2023


  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine


John Wiley & Sons


  • Published Version (Version of Record)