Julius Wolff Institut (JWI) - Center for Musculoskeletal Biomechanics and Regeneration 

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Cell Biology

The research group "Cell Biology" investigates the biology of adult stem cells, immune cells, endothelial precursors and fibroblasts as well as their possible role in musculoskeletal tissue regeneration. We are looking at the interaction between cells, mechanics and the extracellular matrix. Furthermore, we are concentrating on alterations of intrinsic cell functions in response to extrinsic stimuli, such as age or an altered immune response. Our long-term goal is to develop new therapeutic approaches to improve musculoskeletal tissue regeneration, especially for impaired healing cases.

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Cell therapies for muscle regeneration

We are investigating the application of adult stem cells to improve the regenerative outcome of skeletal muscle tissues after severe trauma using clinically relevant animal injury models.

To improve muscle regeneration, different cell types of myogenic or non-myogenic origin have been experimentally tested. These include quiescent (quiescent) or activated muscle progenitor cells (SCs) or differentiated myoblasts from the patient's muscle tissue. Muscle-derived stem cells (MDSCs) may be useful when the injury involves the junction between muscle and associated tendon. These cells are multipotent and can potentially differentiate into fibroblasts or tenocytes. Pericytes and mesoangioblasts from blood vessels within the muscle tissue can differentiate into muscle fibers, but also enhance healing via paracrine mechanisms. Cells with a non-myogenic origin, such as bone marrow mesenchymal stromal cells (BM-MSCs) or adipose tissue (ASCs), can stimulate regeneration via paracrine signaling and/or immunomodulation, while the technology of reprogramming adult somatic cells to the induced pluripotent stem cells (iPSCs) enables the generation of new cells of the myogenic lineage. (Image: Qazi et al., Journal of Cachexia, Sarcopenia and Muscle, Volume: 10, Issue: 3, Pages: 501-516, 2019)

Skeletal muscles have a high healing potential, but this natural regeneeration process, however beyond a certain degree of severity this natural process is insufficient to restore tissue structure and function,  leading to fatty degeneration, scarring and limited muscle function. Severe muscle damages are common and not only a direct consequence of accidents or sports injuries, but also a result of iatrogenic muscle damages produced during of various surgical procedures. The consequences for the affected patients are often very serious and associated with severe physical impairments, such as limping or pain.

Our work is motivated by an acute lack of viable treatment options to treat severe. Together with our clinical partners at the Charité Center for Musculoskeletal Surgery (CMSC), we analyze the time course of muscle healing depending on the severity, in terms of structural and functional recovery of the injured tissue. We use this knowledge to develop appropriate targeted cell-based therapies. We are particularly interested in the use of mesenchymal progenitor cells from different tissues and their unique trophic and immunomodulatory properties to enhance muscle healing.

In close collaboration with our clinical colleagues, we have shown that direct injection of mesenchymal progenitor cells (MSC) into injured muscle reduces local inflammatory response and subsequently significantly improves muscle function. These encouraging preclinical results have already been confirmed in a phase I / II human clinical trial (T. Winkler et al. J Cachexia Sarcopenia Muscle. 2018) and are currently validated in a corresponding phase III trial (HipGen, EU Horizon 2020). The main focus of this research group is to decipher the actual mechanism of action of the transplanted cells and to develop appropriate biomarkers to monitor the success of the therapy (collaboration Prof. Parolini, CREM, Italy). Another goal of our work is to develop appropriate strategies to assess and control hemocompatibility and optimize cell delivery to increase the efficiency and safety of such therapies (Qazi et al. JSCM 2019, Qazi et al. Biomaterials 2015; Moll et al. Trends Mol Med. 2019). Together with our partners at the Wyss Institute at Harvard University (Boston, USA), we have also developed novel biomaterial-based strategies to further increase the efficiency and safety of cell-based therapies (e.g., Qazi et al. Biomaterials 2020, Pumberger et al. Biomaterials 2016 & Qazi et al. Biomaterials 2017; Xing et al. Materials Science and Engineering 2019).