Cellular and molecular basis for tendon repair and regeneration using axolotl as model system

• Applicant: Professor Prayag Murawala, Ph.D.
• Subject Area: Developmental Biology ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429469366

Tendons transmit force from muscles to the bone and are essential for body movements. With an aging population, the incidence of tendon ruptures increases substantially. Consequences are pain and dismobility in the affected patients. Current strategies to treat acute tendon injuries or degenerative tendinopathies focus on surgical stitching and the concomitant activation of existing cells embedded in the tendon, the so-called tenocytes to promote tendon regeneration and restore tendon function. Our previous work suggests loose connective tissue (LCT) cells – dermal and interstitial fibroblasts - as an alternative progenitor cells and eventually more powerful source to repair tendon structures during axolotl limb regeneration. In this proposal, using axolotl as a model, we plan to explore the cellular and molecular basis that determine LCT-to-tendon lineage commitment and thus aim to provide novel regenerative strategy. Moreover, little is known on how this lineage commitment is influenced by its surrounding tissue. Therefore, we aim at characterizing the regeneration-promoting properties of the surrounding extracellular matrix (ECM) in parallel. Understanding mechanisms that axolotls employ to utilize the alternative source cells for tendon repair may eventually lay foundations to improve long-term current strategies of tendon repair in humans.

• DFG Programme: Research Grants