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.

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Severely injured skeletal muscle tissues suffer from necrotic muscle fibers, accumulation of fatty scar tissue and therefore a loss in muscle function. Left alone, the native healing processes are unable to efficiently repair traumatized muscle tissue. In our group, we focus on reinforcing the native healing processes by delivering desirable proteins and cells using porous and injectable biomaterial scaffolds.

Our work is motivated by an acute lack of viable treatment options to treat muscle injuries and promote their regeneration in the clinic. Together with our clinical partners at the Charité Center for Musculoskeletal Surgery (CMSC), we have developed a clinically relevant muscle injury model that consists of multiple severe crush trauma in soleus muscles of Sprague Dawley rats. We use this model to investigate the efficacy of various cell, growth factor, and biomaterials based therapies and analyze the time course of regeneration, in terms of functional recovery of contractile strength as well as structural remodeling of injured tissues. We are particularly interested in using MSCs (Mesenchymal Stromal Cells = adult stem cells) to identify and exploit their unique trophic and immunomodulatory properties. Our research activities have led us to identify unique microenvironments presented by biomaterials that can enhance the therapeutic effects of MSCs in vitro. We are currently extending, these findings in vivo to assess whether the combination of MSCs and a biomaterial is sufficient to a) restore structural tissue integrity, b) to support MSC survival and secretion and c) enhance the overall efficiency of the treatment (Fig.). Concurrently, we aim to evaluate the role of the injury environment in muscle healing and how this is altered by MSC-transplantation by using human biopsies and animal models. The comparison of the obtained human data with the more dedicated results from our animal model will help to determine if paracrine signaling is the dominant mode of action of the MSCs in muscle regeneration.

With our collaborators at the Freie Universität Berlin, we also investigating the paracrine effects of MSCs on muscle cell populations including satellite cells and fibro/adipogenic progenitor cells using mechanically mimetic hydrogel platforms.

Collectively, this should enable us to further characterize the dominant mode of action of MSCs and potentially identify new therapeutic targets, e.g. targeted depletion of specific immune cells or other molecular biological interventions.