Model Systems for Regenerative Therapies

The research group Model Systems for Regenerative Therapies leverages interdisciplinary approaches to interdisciplinary and translational research. Our goal is to improve our mechanistic pathophysiological understanding regarding musculoskeletal fibrosis to a level where we can offer effective solutions for clinical applications.

For this, we use clinical research as indicators for specific patient populations, then study these in detail through mechanistic model systems, and thereafter engineer regenerative therapies within the musculoskeletal field. Our research is mainly focused on studying different aspects of the dynamic process fibrosis, scar tissue formation. Fibrosis is typically initiated by some sort of stress, such as injury, and is the result of failed tissue regeneration that is typically followed by the onset of degenerative diseases.

It is currently not known why certain injuries fail to heal, including those in the synovial joint. One of the most challenging aspects to study this is the lack of a healthy regenerative environment, that can be used as control or baseline. As a result, the failed regenerative environment can mainly be compared to a healthy control environment, leading to a lack of understanding what kind of processes regenerative therapies need to steer. To overcome this, we investigate patient-derived samples to identify the clinical environment in defined patient populations. Next, we use this information in the development of in vitro and in vivo model systems to further study underlying mechanisms and to test our hypothesis. In a final stage, we translate the obtained findings into regenerative therapies to steer failing regenerative environments to functional healing. 

The initial damage in the joint leads to an immediate activation of the innate immune system where pro-inflammatory cells are recruited for phagocytosis and debris removal at the defect site. Next, these cells recruit the pro-regenerative inflammatory cells in order for functional regeneration to occur. It has been suggested that the cellular signaling cascades that steer the balance between the type, polarization and subsequent action of the recruited inflammatory cells regulated the fate of healing. Fibrosis affects the local and systemic immune systems, local tissue-specialized cells and their progenitors, cells from the vascular environment and well as cells from the peripheral nervous system. In addition, mechanical forces are potentially playing a crucial role in both the initiation and progression of finrosis. Since organ functions as local systems under regulation by the central and peripheral nervous system and vasculature, we are targeting our research efforts to understand how these interactions function during homeostasis and disease.