miRNA analysis to discover fracture related biomarkers 2
Biomarkers predictive of fracture healing outcomes would provide a useful tool to allow surgeons to proactively make patient based clinical decisions. Currently, even in high risk groups, there are no accurate ways to determine the potential of a particular patients risk of delayed or non-union. Development of a predictive tool would enable more reliable patient stratification, thus allowing for earlier diagnosis and increasing the potential success of additional early interventions by the surgeon.
In a previous AOTrauma project (MiDiag) we investigated and correlated changes in small non-coding RNA profiles in fracture patients and during osteogenic differentiation. A panel of prospective markers were identified, and this now requires further validation. In addition, we aim to use the methods developed, and the database of patient serum non-coding RNA created, to further investigate markers that are mechanically regulated and would be associated with secondary bone healing.
Della Bella E, Menzel U, Basoli V, Tourbier C, Alini M, Stoddart MJ. Differential Regulation of circRNA, miRNA, and piRNA during Early Osteogenic and Chondrogenic Differentiation of Human Mesenchymal Stromal Cells. Cells. 2020, 9(2):398. doi: 10.3390/cells9020398
Manuel Herzog. Identification of microRNAs involved in mechanically driven differentiation of human mesenchymal stromal cells. Master of Science ETH in Health Sciences and Technology (MSc ETH HST). March 2021. Supervisors: Prof. Dr. Marcy Zenobi-Wong, ETH Zurich; Prof. Dr. Martin Stoddart, AO Research Institute Davos.
Breulmann FL, Hatt LP, Schmitz B, Wehrle E, Richards RG, Della Bella E, Stoddart MJ. Prognostic and therapeutic potential of microRNAs for fracture healing processes and non-union fractures: A systematic review. Clin Transl Med. 2023;13(1):e1161. https://doi.org/10.1002/ctm2.1161
Miclau K, Hambright WS, Huard J, Stoddart MJ, Bahney CS. Cellular expansion of MSCs: Shifting the regenerative potential. Aging Cell. 2022;epub Dec 19:e13759. https://doi.org/10.1111/acel.13759
Breulmann FL, Ramasamy S, Herzog M, Pandian GN, Della Bella E, Stoddart MJ. Differentially expressed microRNAs during early endochondral differentiation of human mesenchymal stromal cells as biomarkers for non-union fractures. 2023 ORS (poster)
Stefano Zaffagnini (Prof), Rizzoli Orthopaedic Institute, Bologna, Italy.
Georg Philipp Mattiassich (Priv. Doz. Dr.), Klinik Diakonissen, Schladming, Austria