Project 8: Development of next-generation cell therapy protocols by exploiting knowledge from regenerating species

The goal of the project is to learn from robustly regenerating organisms how to enhance the ability of mammalian (mouse and human) stem/progenitor cells of the mesoderm to engraft and repair skeletal and cardiac muscle in different forms of muscular dystrophy.  Clinical protocols of cell therapy show currently little efficacy for most mesoderm tissues (Cossu et al. Lancet 2018), due to poor survival, proliferation, migration and integration into the host tissue. These functions are far more efficient in organisms that regenerate efficiently than in mammals. The project aims to express or silence genes (or non-coding RNA) that share homology with genes known to orchestrate regeneration in lower phila in mesoderm progenitor cells such a mesoangioblasts (vessel-associated myogenic progenitors: Dellavalle et al. Nat Cell Biol. 2007). Robust regulatory controls will ensure that the transgene can be activated or silenced as needed. Transduced cells will be challenged in mouse models of acute regeneration and of muscular dystrophies, including immune deficient dystrophic mice that allows transplantation of human progenitors and analysis of their efficacy or possible toxicity.