Potential Therapies Using Myogenic Stem Cells Combined with Bio-Engineering Approaches for Treatment of Muscular Dystrophies

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.

Keywords: dystrophy; regeneration; skeletal muscle; stem cells; therapy.

Figure 1

Therapeutic models for treatment of muscle diseases using myogenic stem cells. Muscle satellite cells, pluripotent stem cells (mesoangioblasts, and CD133+ cells) and ES/iPS cell-derived myogenic stem cells are possible cell sources for MD transplantation therapy. To generate a high yield of stem cells with myogenic potential, isolated cells are expanded by culture with ECM components or using hydrogel biomaterials. For allogeneic transplantation, isolated myogenic stem cells from MD patients are subjected to genetic correction. In addition to typical cell transplantation therapy, the implantation of bioengineered skeletal muscle tissues produced by myogenic stem cells is a promising approach.