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

• Final Report Year: 2024

Final Report Abstract

Tendons transmit the forces generated by muscles to the bones and are therefore an essential part of body movements. As the population ages, the number of tendon ruptures increases dramatically. The result for patients is pain and limited mobility. Current strategies for treating acute tendon ruptures or degenerative tendon diseases focus on surgically suturing both tendon ends together and the associated activation of the cells already in the tendon tissue, the so-called tenocytes, through which tendon regeneration is promoted and tendon function is restored. In our last publication we were able to show that so-called loose connective tissue cells (LCT cells) - dermal and interstitial fibroblasts - may represent an alternative and possibly even more effective precursor cell type for regenerating tendon structures during axolotl limb regeneration. In this research proposal, we aim to investigate the cellular and molecular basis by which LCT cells transform into tendon cells in the axolotl, ultimately developing new regenerative strategies for tendon regeneration. Furthermore, little is known about the extent to which the transformation of LCT cells into tendon cells is influenced by the surrounding cell tissue. Therefore, we also aim to investigate the influence of the extracellular matrix (ECM) surrounding the LCT cells on the conversion of the LCT cells into tendon cells and thus on tendon regeneration. Through our research project, we would like to investigate alternative cell types for tendon regeneration and thus potentially lay a new foundation for new long-term strategies for tendon regeneration in humans.

Publications

• Gene and transgenics nomenclature for the laboratory axolotl—Ambystoma mexicanum. Developmental Dynamics, 251(6), 913-921.
  Nowoshilow, Sergej; Fei, Ji‐Feng; Voss, S. Randal; Tanaka, Elly M. & Murawala, Prayag
  
• The use of transgenics in the laboratory axolotl. Developmental Dynamics, 251(6), 942-956.
  Tilley, Lydia; Papadopoulos, Sofia‐Christina; Pende, Marko; Fei, Ji‐Feng & Murawala, Prayag
  
• A hybrid open-top light-sheet microscope for versatile multi-scale imaging of cleared tissues. Nature Methods, 19(5), 613-619.
  Glaser, Adam K.; Bishop, Kevin W.; Barner, Lindsey A.; Susaki, Etsuo A.; Kubota, Shimpei I.; Gao, Gan; Serafin, Robert B.; Balaram, Pooja; Turschak, Emily; Nicovich, Philip R.; Lai, Hoyin; Lucas, Luciano A. G.; Yi, Yating; Nichols, Eva K.; Huang, Hongyi; Reder, Nicholas P.; Wilson, Jasmine J.; Sivakumar, Ramya; Shamskhou, Elya ... & Liu, Jonathan T. C.
  
• Baculovirus Production and Infection in Axolotls. Methods in Molecular Biology, 369-387. Springer US.
  Murawala, Prayag; Oliveira, Catarina R.; Okulski, Helena; Yun, Maximina H. & Tanaka, Elly M.
  
• Regeneration in Anamniotic Vertebrates. Stem Cell Biology and Regenerative Medicine, 165-192. River Publishers.
  Knapp, Dunja
  
• Collagen IV of basement membranes: II. Emergence of collagen IVα345 enabled the assembly of a compact GBM as an ultrafilter in mammalian kidneys. Journal of Biological Chemistry, 299(12), 105459.
  Pokidysheva, Elena N.; Redhair, Neve; Ailsworth, Octavia; Page-McCaw, Patrick; Rollins-Smith, Louise; Jamwal, Vijayishwer Singh; Ohta, Yuko; Bächinger, Hans Peter; Murawala, Prayag; Flajnik, Martin; Fogo, Agnes B.; Abrahamson, Dale; Hudson, Julie K.; Boudko, Sergei P. & Hudson, Billy G.