Editorial: Stem Cell Therapy for Hereditary Neuromuscular Diseases

Katsumasa Goto^1*Atsushi Asakura^2*

• ¹Toyohashi Sozo Daigaku, Toyohashi, Japan
• ²University of Minnesota Medical School, Minneapolis, United States

The regulation of satellite cell functions is governed by a dual approach that includes both internal and external factors. The microenvironment of stem cells influences the external component, referred to as the stem cell niche (Verma et al., 2018;Hung et al., 2023). To ensure the maintenance of satellite cells throughout their lifespan, various niche cell types coordinate in a spatiotemporally precise manner, regulating quiescence maintenance, self-renewal, and the trajectory of terminal differentiation. Satellite cells are situated within a complex three-dimensional (3-D) environment that includes multiple adjacent niche cells, which are essential for proper cellular function. These neighboring cells, such as mesenchymal progenitor cells, fibroblast-adipocyte progenitor cells (FAP), macrophages, eosinophils, T cells, vascular endothelial cells, and perivascular cells, are acknowledged as pivotal regulators of satellite cells and regenerative processes (Verma et al., 2018;Hicks et al, 2023;Majchrzak et al., 2024). Signals from niche cells that govern control include the extracellular matrix (ECM), growth factors, and interactions between cells (Schüler et al., 2022;Chrysostomou et al., 2024;Helzer et al., 2024). Therefore, it is crucial to understand how aging and disease affect the stem cell niche and to examine the development of therapies based on stem cells.Inherited neuromuscular disorders comprise a diverse array of genetic conditions that affect motor neurons, peripheral nerves, skeletal muscles, or the neuromuscular junction. These disorders are major factors contributing to mortality, disability, and mental health issues globally, rendering them a significant public health challenge. One notable example is Duchenne muscular dystrophy (DMD), the most prevalent type of muscular dystrophy, which is a severe X-linked disorder marked by mutations in the dystrophin gene. These genetic alterations lead to the creation of defective dystrophin-related glycoprotein complexes (DGCs) within satellite cells and skeletal muscle fibers (Robertson et al., 2024;Łoboda and Dulak, 2025). The lack of functional dystrophin causes improper muscle regeneration and heightens the myofibers' vulnerability to injury, enhancing the disease's progressive nature. Eventually, satellite cells reach a tipping point at which they can no longer keep pace with the degeneration of muscle fibers in dystrophic muscles, thereby advancing the disease. Progress in genetic studies since the discovery of the DMD gene in 1986 has revealed countless disease-causing mutations (Monaco et al., 1986); however, effective therapies are still scarce. Thus, the emergence of new treatments, especially those focusing on stem cell-based regenerative medicine, is of paramount importance. This Research Topic seeks to shed light on the most recent breakthroughs in treatment strategies for hereditary neuromuscular disorders, focusing on muscle stem cell therapy and other novel therapeutic approaches relevant to conditions such as DMD. This Research Topic delved into the biological mechanisms underlying these disorders, the clinical applications of regenerative medicine, and the future opportunities offered by innovative therapies. Furthermore, this Research Topic investigated intricate multicellular interactions within muscle tissues by employing advanced methodologies, including high-resolution imaging, systems biology, proteomics, and epigenetics.Four original review articles were published on this Research Topic. Spatial Transcriptomics has emerged as a revolutionary technology poised to reshape and accelerate our understanding of cellular communication. This aspect is particularly significant in skeletal muscle, where syncytial myofibers exist alongside a diverse array of interstitial cell populations. In the first manuscript, Virtanen et al. investigated the different types of Spatial Transcriptomics methods, provided a concise overview of available analytical tools, and emphasized recent progress in the skeletal muscle field enabled by Spatial Transcriptomics. Stem cell therapy for DMD is a promising approach to promote muscle regeneration, though the conditions for transplantation and the pretreatment of various cell types remain under refinement. The second manuscript, by Tominari et al., outlined the obstacles to effective muscle tissue regeneration in DMD and examined the most recent developments in stem cell-based therapy for the condition. They summarized strategies for preconditioning cells for replacement therapies and for treating the disease niche to enhance muscle fiber integration. Multiple sclerosis (MS), a persistent autoimmune disorder affecting the central nervous system (CNS) and skeletal muscle, is marked by inflammation, demyelination, and neurodegeneration, resulting in a variety of clinical manifestations such as fatigue, sensory deficits, and cognitive impairment. The third manuscript, by Sheikhi et al., provided a comprehensive analysis of mesenchymal stem cells (MSCs) for cell therapy in MS, examining mechanisms of action encompassing immune system regulation, remyelination facilitation, and neuroregeneration. Particular emphasis was placed on challenges such as delivery methods, dosing protocols, and the integration of MSCs with traditional treatments.Recent technological advancements in imaging, such as confocal, intravital, and multiphoton microscopy, offer promising avenues for observing and delineating the dynamic morphology and behavior of satellite cells. The fourth manuscript, by Karthikeyan and Asakura, summarized live and 3-D imaging techniques that have advanced understanding of satellite cell activities, morphological alterations, interactions within the muscle microenvironment, and internal signaling networks during the transition from quiescence to activation. By merging cutting-edge imaging technologies with computational approaches, researchers can explore complex biological processes underlying skeletal muscle regeneration and associated degenerative conditions such as sarcopenia and DMD. This collection of four articles showcases the exceptional caliber of the writings featured in the Research Topic of the Stem Cell Research segment of Frontiers in Cell and Developmental Biology. It unveils a research domain advancing at an impressive rate.