Journal Article


Daniel J Kelly
Adam O'Reilly



computational model tissue differentiation environmental factors stem cell mesenchymal stem cell fate osteochondral defect repair cell proliferation oxygen

The role of oxygen as a regulator of stem cell fate during the spontaneous repair of osteochondral defects. (2015)

Abstract The complexity of the in vivo environment makes it is difficult to isolate the effects of specific cues on regulating cell fate during regenerative events such as osteochondral defect repair. The objective of this study was thus to develop a computational model to explore how joint specific environmental factors regulate mesenchymal stem cell (MSC) fate during osteochondral defect repair. To this end, the spontaneous repair process within an osteochondral defect was simulated using a tissue differentiation algorithm which assumed that MSC fate was regulated by local oxygen levels and substrate stiffness. The developed model was able to predict the main stages of tissue formation observed by a number of in vivo studies. Following this, a parametric study was conducted to better understand the dramatic impact on osteochondral healing reported in experimental studies where the rate of angiogenesis was altered. In the simulations where angiogenesis was reduced, by week 12, the subchondral plate was predicted to remain below the native tidemark, while the chondral region was composed entirely of cartilage and fibrous tissue. In the simulations where angiogenesis was increased, more robust cell proliferation and cartilage formation were observed during the first 4 weeks, however by week 12 the subchondral plate had advanced above the native tidemark while any remaining tissue was either hypertrophic cartilage or fibrous tissue. These results suggest that osteochondral defect repair could be enhanced by interventions where angiogenesis is promoted but confined to within the subchondral region of the defect. This article is protected by copyright. All rights reserved.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Daniel J Kelly, Adam O'Reilly

Experts in our system

Daniel Kelly
Trinity College Dublin
Total Publications: 190
Adam O'Reilly
Royal College of Surgeons in Ireland
Total Publications: 4