Stem Cell Differentiation Toward the Myogenic Lineage for Muscle Tissue Regeneration: A Focus on Muscular Dystrophy

Abstract

Skeletal muscle tissue engineering is one of the important ways for regenerating functionally defective muscles. Among the myopathies, the Duchenne muscular dystrophy (DMD) is a progressive disease due to mutations of the dystrophin gene leading to progressive myofiber degeneration with severe symptoms. Although current therapies in muscular dystrophy are still very challenging, important progress has been made in materials science and in cellular technologies with the use of stem cells. It is therefore useful to review these advances and the results obtained in a clinical point of view. This article focuses on the differentiation of stem cells into myoblasts, and their application in muscular dystrophy. After an overview of the different stem cells that can be induced to differentiate into the myogenic lineage, we introduce scaffolding materials used for muscular tissue engineering. We then described some widely used methods to differentiate different types of stem cell into myoblasts. We highlight recent insights obtained in therapies for muscular dystrophy. Finally, we conclude with a discussion on stem cell technology. We discussed in parallel the benefits brought by the evolution of the materials and by the expansion of cell sources which can differentiate into myoblasts. We also discussed on future challenges for clinical applications and how to accelerate the translation from the research to the clinic in the frame of DMD.

Enhanced skeletal muscle formation on microfluidic spun gelatin methacryloyl (GelMA) fibres using surface patterning and agrin treatment

“…In accordance with these findings, we also observed increased expression of the dystrophin gene in agrin‐treated C2C12 on GelMA fibres (Figure ). Dystrophin, a member of the dystrophin‐associated protein complex, attaches to both cytoskeletal actin and the transmembrane protein β‐dystroglycan, which binds through its extracellular domain to α‐dystroglycan, which in turn binds to the muscle basal lamina via laminin (Ostrovidov et al, ). Thus, the dystrophin‐associated protein complex connects the ECM to the intracellular cytoskeleton, providing mechanical stability to the sarcolemma and protecting contracting myotubes from disruption (Montanaro, Lindenbaum, & Carbonetto, ).…”

Anisotropic Materials for Skeletal‐Muscle‐Tissue Engineering

“…[40, 41] Finally, pluripotent stem cells also represent a potential progenitor cell source when differentiated into myogenic progenitor cells (MPCs). [42, 43] …”

3D Bioprinting in Skeletal Muscle Tissue Engineering

“…Especially, the engineering of muscle fibers in vitro requires the culture of myoblasts in an anisotropic environment, promoting their alignment, favoring their fusion and the myogenesis . Different methods have been developed to induce cell alignment such as the use of grooves/ridges micro/nanopatterned substrates, nanofibers, anchors and hydrogel compaction, chemical surface patterning, stencils, mechanical stimulations, and electrical or magnetic fields . Moreover, to improve skeletal muscle cell differentiation and to obtain muscle tissues with high functionality, scaffolds with specific topographical features, stiffness, electrical conductivity, polymeric compositions (i.e., homopolymer, composites, hybrid nanomaterials‐polymer blend), and soluble factors have been developed .…”

“…Skeletal muscle tissue engineering (SMTE) aims to replace or to restore functionality in skeletal muscles that have been damaged or have lost some of their functionalities due to diseases, accidents, or severe surgeries. SMTE involves the culture of myogenic progenitor cells or stem cells obtained from the patient, the use of a scaffold in some cases or could be scaffold‐free in others, and the generation of a functional skeletal muscle that can be implanted into the patient's body . SMTE has applications in regenerative medicine but also in cell‐based assays, biorobotics, biosensing, energy harvesting, and drug screening .…”

“…SMTE involves the culture of myogenic progenitor cells or stem cells obtained from the patient, the use of a scaffold in some cases or could be scaffold-free in others, and the generation of a functional skeletal muscle that can be implanted into the patient's body. [7] SMTE has applications in regenerative medicine [8] but also in cell-based assays, [9] biorobotics, biosensing, energy harvesting, and drug screening. [10][11][12][13] In this Ali Khademhosseini, Ph.D., is the Levi Knight Professor of Bioengineering, Chemical Engineering and Radiology at UCLA.…”