Study identifies potential therapeutic target for bone repair in adults with severe injury or disease

Study opens new avenues for bone repair in adults with severe fractures and bone degeneration

Irish scientists are developing an advanced technology to speed up bone repair in adults who have suffered severe fractures and bone degeneration. This follows the identification of a gene which explains why children’s stem cells form bone very quickly.

Scientists at RCSI (Royal College of Surgeons in Ireland) and SFI funded AMBER (Advanced Materials and BioEngineering Research) centre, in collaboration with clinicians at the National Paediatric Craniofacial Centre (NPCC) at Temple Street Children’s University Hospital, compared children and adult-derived stem cells in order to understand more comprehensively why children’s cells have an extraordinary capacity to respond to their environment and repair bone quickly.

Their study investigated the age-associated changes in the capacity of stem cells to form bone tissue, and identified a potential therapeutic target which opens new avenues to develop novel therapeutic target-specific biomaterials for restoring a child-like bone healing capacity in adults suffering from severe fractures and bone degeneration.

The RCSI and AMBER team carried out the study with Mr. Dylan Murray, lead clinician at the NPCC at Temple Street Children’s University Hospital.

In this study the researchers found that children’s stem cells are far more sensitive to changes in their physical environment and form bone quicker than adult-derived stem cells. Furthermore, by comparing the genetic expression of children and adult-derived stem cells, the researchers identified a particular gene (JNK3) that explains why children’s stem cells respond to their physical environment differently, creating more bone than adult cells, thus, suggesting its potential as a new target to promote enhanced bone repair.  Building on a wealth of experience in advanced biomaterials in the RCSI Tissue Engineering Research Group (TERG), the team is now utilising this knowledge to develop an advanced technology to facilitate enhanced bone repair.

Professor Fergal O’Brien from the Department of Anatomy in RCSI who is lead-Principal Investigator on the project and Deputy Director of AMBER said: ‘We are very excited by the identification of a key mechanism which influences bone formation in children and this study opens a new research avenue which will focus on therapeutic delivery in order to upregulate this gene with a view to replicating the enhanced bone regenerative potential of children in adults. Ultimately we hope that this research will lead to improved treatments for patients who have suffered severe bone loss through injury or disease’.

Commenting on the significance of the research, Dr Arlyng Gonzalez Vazquez, joint first author on the study said:

Our findings not only have major implications for tackling the decrease of bone repair capacity that occurs with age but also set the basis for a novel research strategy applicable to other tissues in the body.

The research, which has just been published in Acta Biomaterialia – a leading journal in the biomedical engineering field, was the result of a multi-disciplinary effort between cell biologists, clinicians and engineers in the RCSI TERG and €58million SFI-funded AMBER Centre. Post-doctoral researchers, Dr Arlyng Gonzalez Vazquez and Dr Sara Barreto, the first authors on the study conducted the research under the supervision of Professor O’Brien in RCSI and Mr. Dylan Murray in Temple Street. This work was supported by the Health Research Board, the Temple Street Foundation (the fundraising arm of the hospital) and the Irish Research Council.

RCSI is ranked in the top 250 institutions worldwide in the Times Higher Education World University Rankings (2016-2017). It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide.