Cell therapies are a promising approach to treat orthopedic diseases, with strong translational progress. However, we still face non-responders, which might be due to maladaptations of the context-sensitive MSCs in the environment of disease. As the extracellular matrix is a crucial player in musculoskeletal tissues, we aim to understand the interactions between the MSCs and the matrix in health and disease on the molecular level to develop targeted regimes that steer cell fate towards regeneration.  

Recent research shows that mitochondria play a central role in MSC regenerative modes of action. We aim to understand these mechanisms, relating cellular metabolism to MSC-mitochondria-driven rescue of damaged cells. Further, we explore mitochondrial transfer mechanisms and their triggers in healthy versus compromised cells.

Defining MSC as accurate as possible is crucial to the understanding and outcome of regenerative therapies. However, current MSC phenotyping approaches, defining the cells as multipotent mesenchymal stromal cells, are insufficiently reflecting the cellular functions and are inadequate for the characterization of MSC from animal species. Harnessing lipidomics and metabolomics, we aim to identify markers that are functionally representative of potent MSC across species.

Due to the context-sensitive nature of MSC, cell culture can strongly alter their properties, impacting on their therapeutic potency. Moreover, routine cultivation protocols are adapted to MSC from the human species, e.g. regarding the cell culture media and supplements or cultivation temperatures. We aim to develop procedures that are applicable with a high level of analogy to cells from different species, while providing species-specific physiological conditions.