Hydrogel Delivery System Shows Promise for Cell-Based Muscular Dystrophy Treatment

Duchenne muscular dystrophy (DMD) is a devastating, incurable muscle-wasting disorder caused by mutations in the dystrophin gene. While cell-based therapies have shown promise, challenges exist in obtaining a sufficient number of stem/progenitor cells with myogenic potential for effective engraftment. While that hurdle can now be addressed thanks to advances in differentiation protocols for human pluripotent stem cells, embryonic stem cells or induced pluripotent stem cells - to generate an unlimited supply of myogenic progenitor cells (MPCs) for transplantation - delivery of donor cells via intramuscular injection is considered invasive and impractical in the clinic since hundreds of injections would be needed to cover large regions of affected skeletal muscle.

In a new study published in Cell Reports Medicine, researchers led by Dr. Yung-Yao Lin at Queen Mary University of London have addressed that delivery challenge by developing a transplantation strategy that combines hydrogel-mediated delivery with CRISPR-corrected human myogenic progenitor cells (MPCs) derived from DMD patient stem cells.

The study, which involved collaborators at UCL Great Ormond Street Institute of Child Health and the Blizard Institute, demonstrated that engineered 3D cell-laden hydrogel constructs successfully engrafted in dystrophin-deficient mdx nude mice without requiring pre-treatment of host muscles. The team reports that the transplanted cells produced full-length dystrophin at both 4 weeks and 5-6 months after transplantation.

Most significantly, human myofibres within the dystrophic mouse muscle were functionally integrated - forming neuromuscular junctions with mouse motor neurons and supported by mouse vasculature. Human PAX7-positive cells also populated the satellite cell niche, suggesting potential for ongoing muscle regeneration.

Encouragingly, the study revealed no evidence of tumorigenesis in mice with long-term engraftment (5-6 months), addressing key safety concerns. These findings provide compelling proof-of-concept for a hydrogel-based cell therapy as a potential treatment for DMD and other muscle-wasting disorders.

Read the full open-access article entitled 'Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment' here.