CELL THERAPY FOR MUSCLE DYSTROPHIES: DELIVERY OF MYOGENIC PRECURSOR CELLS AND AMNIOTIC STEM CELLS VIA POLYMERIC SCAFFOLDS

Cell therapy represents a promising approach for the treatment of muscular dystrophies. So far, promising results have been obtained both with stem cells, delivered via blood stream, and myogenic cells isolated from adult muscle tissue. However, each approach published so far still presented unresolved issues and no definitive protocol has been developed. The different problems that have to be solved can be grouped into two main categories: the identification of the most suitable cell type/source (i.e., easily available and ethically acceptable) and the best delivery route. The project presented here proposes to use two distinct cell types, both of which fulfill these requirements: muscle cells derived from biopsies and cultured in vitro and stem cells derived from amniotic fluid (like those routinely used for pre-natal diagnosis). Cells will be delivered into the muscles of dystrophic mice with a novel approach, based on the implant in the diseased muscles of biocompatible scaffolds (sort of soft tiny sponges) onto which cells have been previously seeded in vitro. Our preliminary results have shown that this approach yielded better results than direct intramuscular injection. Besides, we will specifically target our protocol towards the introduction of myogenic cells into the diaphragm, something that no delivery protocol has achieved so far. Our biopolymer processing methods have been developed considering technical, economical and clinical perspectives, essential prerequisites for industrial technology transfer and scale-up production. Our findings will also be of great importance towards the design and development of injectable, cellularized scaffolds, a technical evolution that will increase even further the therapeutic potential of our approach. In summary, the results of our project will provide a valuable basis for the development of actual clinical protocols for muscular dystrophies.