Finalist EPFL doctorate Award 2018 – Laura Lukjanenko
© 2018 EPFL
Special distinction from the selection committee to Laura Lukjanenko for her thesis “Novel interventions to recover the regenerative capacity of aged skeletal muscle by targeting the interactions in the stem cell niche”
Thesis n°7144(2016)
Thesis directors: Dr J. Feige, Prof. J. Auwerx
The ability of skeletal muscle to regenerate upon injury is conferred by tissue-resident stem cells called satellite cells. With age, the regenerative capacity of muscle stem cells (MuSCs) dramatically declines. Developing strategies to enhance muscle repair in elderly people is therefore required; in particular to accelerate their recovery from injuries following falls or from surgical interventions affecting muscle tissues.
Aging is a multisystemic process that requires a global therapeutic approach. Likewise, the thesis describes points of actions at three levels of the MuSC niche to successfully rescue multiple dysfunctions of aged MuSCs:
- Treating aged muscles with Fibronectin to ameliorate the extracellular matrix remodeling during muscle repair.
- Restoring cellular crosstalk within the niche through WISP1 treatment; a protein secreted by niche support cells called Fibro-Adipogenic Progenitors during muscle repair and responsible for promoting MuSC regenerative function.
- Acting at the systemic level through the rescue of age-related drop of Apelin circulating levels.
Our work opens new approaches for interventions and provides evidence that targeting MuSC interactions with their niche is a promising strategy to restore regenerative function. Our findings and the underlying concepts also bear potential for extension to other adult stem cell niches in tissues with high regenerative potential.
