In a mouse model of muscular dystrophy, researchers in the UK announced a clinically applicable transplantation method that uses CRISPR-corrected human myogenic cells in hydrogels to produce viable muscle tissue.
Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a debilitating and incurable muscle-wasting condition. Despite the potential of cell-based therapies, it is difficult to obtain enough stem/progenitor cells with myogenic potential for successful vaccination.
Hydrogel Delivery System
In order to produce an infinite supply of myogenic progenitor cells (MPCs) for transplantation, that obstacle can now be overcome thanks to advancements in differentiation protocols for human pluripotent stem cells, embryonic stem cells, or induced pluripotent stem cells. However, intramuscular injection of donor cells is regarded as invasive and impractical in the clinic because hundreds of injections would be required to cover large regions of affected skeletal muscle.
Researchers at Queen Mary University of London, under the direction of Dr. Yung-Yao Lin, have developed a transplantation strategy that combines hydrogel-mediated delivery with CRISPR-corrected human myogenic progenitor cells (MPCs) derived from DMD patient stem cells in order to overcome that delivery challenge. Their findings were recently published in Cell Reports Medicine.
Full-length dystrophin
The Blizard Institute and UCL Great Ormond Street Institute of Child Health collaborated on the work, which showed that manufactured 3D cell-laden hydrogel constructions successfully engrafted in dystrophin-deficient mdx nude mice without the need for host muscle pretreatment. Full-length dystrophin was created by the transplanted cells at 4 weeks and 5–6 months post-transplantation, according to the team.
The most important finding was that human myofibres were functionally integrated into the dystrophic mouse muscle, making neuromuscular connections with mouse motor neurons and being maintained by mouse vasculature. Additionally, human PAX7-positive cells filled the satellite cell niche, indicating the possibility of continuous muscle regeneration.
Fortunately, the study addressed important safety concerns by finding no indication of cancer in mice with long-term engraftment (5–6 months). With regard to DMD and other muscle-wasting illnesses, these results offer strong proof-of-concept for a hydrogel-based cell therapy.
Learn More: Potential Upcoming New Gene Therapies for Duchenne Muscular Dystrophy
