Abstract
Muscular dystrophies (MDs) are a group of heterogeneous genetic disorders caused by mutations in the genes encoding the structural components of myofibres. The current state-of-the-art treatment is oligonucleotide-based gene therapy that restores disease-related protein. However, this therapeutic approach has limited efficacy and is unlikely to be curative. While the number of studies focused on cell transplantation therapy has increased in the recent years, this approach remains challenging due to multiple issues related to the efficacy of engrafted cells, source of myogenic cells, and systemic injections. Technical innovation has contributed to overcoming cell source challenges, and in recent studies, a combination of muscle resident stem cells and gene editing has shown promise as a novel approach. Furthermore, improvement of the muscular environment both in cultured donor cells and in recipient MD muscles may potentially facilitate cell engraftment. Artificial skeletal muscle generated by myogenic cells and muscle resident cells is an alternate approach that may enable the replacement of damaged tissues. Here, we review the current status of myogenic stem cell transplantation therapy, describe recent advances, and discuss the remaining obstacles that exist in the search for a cure for MD patients.
Highlights
Muscular dystrophies (MDs) consist of several genetic diseases that are caused by a variety of mutations in structural proteins, and that result in progressive degeneration and weakness due to muscle damage, inflammation, or deposition of adipose and fibrotic tissue [1]
These studies were followed by a phase I clinical trial, where allogeneic myoblasts were transplanted into Duchenne muscular dystrophy (DMD) patients, and as expected, dystrophin protein expression was derived from transplanted cells [20,21,22,23]
Tremendous progress has been made in addressing the challenges of conventional cell therapy through a combination of gene modifications and bioengineering approaches
Summary
Muscular dystrophies (MDs) consist of several genetic diseases that are caused by a variety of mutations in structural proteins, and that result in progressive degeneration and weakness due to muscle damage, inflammation, or deposition of adipose and fibrotic tissue [1]. MD therapies, including exon skipping, stop codon read-through, and viral vector-based approaches, are most advanced for DMD, and some have progressed to the clinical trial stage [14,15]. These treatments have limited efficacy as well as the potential to elicit adverse immune responses and are unlikely to be curative. We describe emerging MD therapies, with a particular focus on stem cell-based therapies, and future treatment prospects
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