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Muscle progenitors, also known as skeletal muscle progenitor cells (SMPCs) or myogenic progenitor cells (MPCs), are stem cells that contribute to muscle regeneration and can differentiate into skeletal muscle. SMPCs are one of the most valuable cell types for treating neuromuscular diseases, such as muscular dystrophy, through cell-based therapy. These progenitors can be isolated from various sources, including adult tissues and pluripotent stem cells. In the context of muscle repair and regeneration, satellite cells, a type of dormant progenitor located at the periphery of skeletal myofibers, play a crucial role. Additionally, muscle fibro-adipogenic progenitors are muscle-resident interstitial cells that contribute to adult muscle homeostasis and regeneration by shaping the microenvironment through the secretion of various factors.
| Characteristics | Values |
|---|---|
| Definition | Muscle progenitors are stem cells that can contribute to muscle regeneration and differentiate into skeletal muscle. |
| Types | Skeletal muscle progenitor cells (SMPCs), also called myogenic progenitors, are one of the most valuable types. |
| Sources | SMPCs have been isolated from pre- or post-natal muscles, non-muscle somatic tissues, and adult tissues. |
| Transplantation | Myogenic progenitor cell transplantation has been studied for muscle regeneration following hindlimb ischemia and reperfusion injury. |
| Therapeutic Applications | Muscle progenitors show potential for treating neuromuscular diseases, such as muscular dystrophy, and regenerating dystrophic muscle. |
| Tissue Repair | Muscle progenitors support tissue repair and regeneration, especially in skeletal muscle, which has a unique ability to regenerate in response to injury. |
| Cell Types | Muscle progenitor cells include satellite cells, side population cells, muscle-derived stem cells, mesenchymal stem cells, and mesoangioblasts. |
| Gene Expression | Muscle progenitors express transcription factors like Pax7, which plays a central role in cell specification, maintenance, and function. |
| Cell Signaling | Tissue-resident mesenchymal progenitors provide signaling cues that modulate other muscle-resident cells' function during regeneration. |
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What You'll Learn
Muscle progenitor specification and myogenic differentiation
Satellite cells are a low-abundance population in muscle tissue, and these cells spontaneously differentiate once isolated. To overcome this obstacle, induced expression of Pax7 in mouse embryonic stem cells (ESCs) is used, from which skeletal muscle progenitors, termed iPax7 cells, are derived. Upon transplantation into dystrophic mice, iPax7 muscle progenitors functionally mimic satellite cells and are able to seed the stem cell niche and ameliorate muscle wasting.
IPax7 progenitors recapitulate the transcriptomic and epigenetic features of satellite cells. They represent a good model for investigating how TF regulates genomic architecture in muscle progenitor cells. To assess genome-wide changes during progenitor specification and differentiation in iPax7 cells, Hi-C and promoter capture Hi-C (pCHi-C) are performed, revealing an extensive three-dimensional (3D) reorganization of chromatin.
By comparing results with data from mouse ESCs and aided by 3D modelling of pCHi-C interactions and proteome-wide capture of Pax7-interacting proteins, enhancer hubs (EnHs) and key promoter-enhancer (P-En) interaction motifs are identified. Two classes of Pax7-associated P-En contacts are discovered, the maintenance of which is either Pax7-dependent or independent. Enhancers from the latter group are associated with the recruitment of additional myogenic TFs and epigenetic memory during differentiation, and they retain their long-range interactions and an open and active state upon the loss of Pax7.
In summary, muscle progenitor specification and myogenic differentiation involve changes in chromatin topology, with key roles played by enhancers, transcription factors, and epigenetic memory. The use of iPax7 cells derived from ESCs provides a valuable model for studying these processes and developing therapeutic strategies for muscle regeneration and repair.
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Muscle progenitor cell transplantation
Muscle progenitor cells, also known as myogenic progenitors, are cells that can contribute to muscle regeneration and differentiate into skeletal muscle. They are valuable for therapeutic applications, particularly in treating neuromuscular diseases. These diseases affect skeletal muscle and/or nervous control, resulting in direct disruption of skeletal muscle or indirect disruption via nervous system dysfunction.
Different types of stem/progenitor cells have been identified as possible resources for muscle progenitor cells, including satellite cells, side population cells, muscle-derived stem cells, mesenchymal stem cells, myogenic pericytes, and mesoangioblasts. Satellite cells, which are present in postnatal muscles, contribute to muscle growth and regeneration and can be defined as resident muscle progenitor cells.
When designing a cell-based therapy, the choice of cell type depends on the specific pathological condition being treated and the environment within the target tissue. The survival of transplanted cells is influenced by the tissue environment, as seen in studies where fully differentiated myoblasts from adult skeletal muscle had lower survival rates in dystrophic muscle compared to undifferentiated stem/progenitor cells.
Myogenic progenitor cell transplantation has been explored in the context of muscle regeneration following hindlimb ischemia and reperfusion injury (IRI). IRI severely affects muscle, and the transplantation of myogenic progenitor cells (MPC) obtained from isolated satellite cells has shown promising results in muscle regeneration. In a study, a clamping model of murine hindlimb ischemia was used to induce IRI in skeletal muscle. After a specified warm ischemic time and reperfusion, MPC expressing reporter proteins were injected intramuscularly. The surface marker expression and differentiation potential of MPC were analyzed in vitro, and in vivo imaging and histopathologic evaluations were performed to quantify cell fate, engraftment, and regeneration.
Overall, muscle progenitor cell transplantation holds potential for therapeutic applications, particularly in treating neuromuscular diseases and muscle regeneration following IRI. Further research is needed to fully understand and optimize these transplantation techniques and their applications.
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Muscle stem cell types
Muscle progenitor cells are stem cells that can contribute to muscle regeneration and differentiate into skeletal muscle. They are valuable for therapeutic applications, especially in treating neuromuscular diseases.
There are two main types of muscle stem cells: satellite cells and adult stem cells. Satellite cells are present in postnatal muscles and contribute to muscle growth and regeneration. They are characterised by the expression of the transcription factor (TF) paired-box 7 (Pax7), which plays a central role in satellite cell specification, maintenance, and function. Satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle.
Adult stem cells, on the other hand, are tissue-specific and can intrinsically maintain, generate, and replace terminally differentiated cells within their specific tissue. They can differentiate into various cell types, such as hematopoietic cells and muscle cells following transplantation.
Other types of stem/progenitor cells that have been identified as possible resources for muscle progenitor cells include side population cells, muscle-derived stem cells, mesenchymal stem cells, myogenic pericytes, and mesoangioblasts.
Additionally, skeletal muscle stem cells (MuSCs) have been identified as resident muscle stem cells that play a crucial role in the remarkable regenerative capacity of skeletal muscle. MuSCs interact with various cell types, including macrophages, fibro-adipogenic progenitors (FAPs), and endothelial cells, which regulate their behaviour and activation.
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Muscle progenitor origins, potency, and heterogeneity
Muscle progenitors, also known as skeletal muscle progenitor cells (SMPCs) or myogenic progenitors, are stem cells that contribute to muscle regeneration and can differentiate into skeletal muscles. They are valuable for therapeutic applications, particularly in treating neuromuscular diseases such as muscular dystrophy.
Origins
The muscle connective tissue's primary components are the extracellular matrix and its resident stromal cells, which continuously reshape it during embryonic development, homeostasis, and regeneration. Fibro-adipogenic progenitors (FAPs) are muscle-resident interstitial cells with mesenchymal stem/stromal cell properties. They are the precursors of specialized cells, including activated fibroblasts, adipocytes, and osteogenic cells, which form after injury.
Potency
SMPCs are tissue-specific stem/progenitor cells, also known as adult stem cells. They intrinsically reside in various tissues of the body and can maintain, generate, and replace terminally differentiated cells within their specific tissue. Mammalian adult skeletal muscle has a robust ability to regenerate, a process dependent on muscle stem cells called satellite cells. Satellite cells express the transcription factor paired-box 7 (Pax7), which plays a central role in their specification, maintenance, and function.
Heterogeneity
The diverse fibroblast nomenclature has led to some confusion in muscle biology literature. Distinguishing true lineage heterogeneity from the diverse functional states that muscle-resident mesenchymal progenitors can acquire remains a priority issue. FAPs exhibit high cellular heterogeneity within their populations in response to injury. In mouse muscles, two major FAP subpopulations (Dpp4 FAPs and Cxcl14 FAPs) are present in homeostatic conditions. The unrestrained activation of progenitor cells and their subsequent differentiation can potentially drive disease development.
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Muscle progenitor therapeutic applications
Skeletal muscle progenitor cells (SMPCs), also known as myogenic progenitors, have been identified as valuable for therapeutic applications. SMPCs can contribute to muscle regeneration and differentiate into skeletal muscles. They are particularly useful for treating neuromuscular diseases, which affect skeletal muscle and/or nervous control, resulting in direct or indirect disruption of muscle function.
For neuromuscular diseases such as muscular dystrophy, stem cell-based therapy targeting degenerating muscles is a promising approach. SMPCs have been isolated from various sources, including pre- and post-natal muscles, non-muscle somatic tissues, and pluripotent stem cells. Satellite cells, a type of SMPC, are present in postnatal muscles and play a crucial role in muscle growth and regeneration. They are characterized by the expression of the transcription factor Pax7, which is involved in cell specification, maintenance, and function.
The choice of cell type for therapeutic applications depends on the specific pathological condition being treated and the target tissue environment. For example, undifferentiated stem/progenitor cells have a higher survival rate in dystrophic muscle compared to fully differentiated myoblasts. This highlights the importance of selecting the most appropriate cell type for successful therapeutic strategies.
Muscle-derived mesenchymal stem and progenitor cells have potential therapeutic applications in tissue engineering and regenerative medicine. They can be obtained through routine biopsy or surgical debridement and have been shown to enhance nerve regeneration. Additionally, these cells are being explored for vascular regeneration, where they promote the proliferation and migration of smooth muscle and vascular endothelial cells.
In summary, muscle progenitor cells, specifically SMPCs, hold great promise for therapeutic applications, particularly in the treatment of neuromuscular diseases and the regeneration of skeletal muscle. Further research and understanding of these cells will contribute to the development of successful therapeutic strategies.
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Frequently asked questions
Muscle progenitor cells are stem cells that can differentiate into skeletal muscle.
SMPCs are used in cell-based therapies designed to treat neuromuscular diseases. They can also be used to study regeneration and repair.
Examples of muscle progenitor cells include satellite cells, myogenic progenitor cells (MPCs), and fibro-adipogenic progenitors.
Satellite cells are dormant progenitors located at the periphery of skeletal myofibers. They can be triggered to proliferate for both self-renewal and differentiation into myogenic cells.
Muscle progenitor cells contribute to muscle regeneration by providing signaling cues that modulate the function of other muscle-resident cells and actively remodeling the extracellular matrix.
