Enhancing therapeutic efficacy of induced pluripotent stem cellderived cellderived myogenic progenitors as a treatment for muscular dystrophy.

Muscular dystrophies (MD) are a group of debilitating muscle disorders for which no cure exist. Within the search for a successful therapy, pluripotent stem cells (PSCs) hold the greatest potential as they have the ability to proliferate extensively. This proliferation opens the possibility to obtain sufficient amount of myogenic progenitors to regenerate the entire muscle pool. Nevertheless, improvements need to be made to work towards a clinical relevant protocol that has an efficacy high enough to allow functional outcome in MD patients.
This PhD project will investigate if manpulation the bone morphogenetic protein (BMP) and Notch receptor signaling pathway can increase therapeutic efficacy of human iPSC-derived mesodermal progenitors (MiPs). Therefore, this proposal aims at (i) converting the MiP protocol towards a clinical translational differentiation protocol, (ii) achieving both pathway manipulations by only using small molecules, (iii) comparing the effect of these pathway manipulation to enhance the myogenic commitment and subsequent therapeutic efficacy of the MiPs (iv) validating the most promising approach in a more clinical relevant setting, namely in the golden retriever MD (GRMD) model.
This project will allow us to create an industrial-applicable protocol that has an efficiency high enough to allow functional outcome in MD patients.