Figure 2 - available via license: Creative Commons Attribution 3.0 Unported
Content may be subject to copyright.
Skeletal muscle consists of muscle fibers bound by connective tissue. The outermost sheath of connective tissue that wraps around the muscle is called the epimysium. Bundles of muscle fibers, called fascicles, are enclosed by the perimysium and each muscle fiber is covered in a thin connective tissue layer called the endomysium that contains the extracellular fluid and nutrients to support the muscle fiber. Reproduced with permission from Springer Nature. Sciorati, C., et al., Cell death, clearance and immunity in the skeletal muscle. Cell Death and Differentiation. 2016;23(6):927-937. DOI: 10.1038/cdd.2015.171.
Context in source publication
Context 1
... main components of ECM are largely conserved across animal species [80,81]. The ECM of skeletal muscle is organized into three layers; the endomysium layer sur- rounds the individual muscle fibers, the perimysium surrounds the bundles of muscle fibers known as fascicles, and the epimysium surrounds the entire muscle (Figure 2). Collagen type I is predominant in the perimysium, whereas collagen type III is prevalent in the endomysium the epimysium [82]. ...
Citations
... The use of ASC in patients with Duchenne muscular dystrophy (who had paralysis and death at around 20 years of age) found that 81% of participants were able to maintain muscle strength and prevention to loss of muscle mass. This is consistent with what is written by Maclean et al. and Dunn et al. that injection of fat into the vocal cords through the side of the thyroarytenoid muscle has the potential to increase muscle strength and mass [17,18]. This property of ASC in fat is suspected to be the main reason for a similar increase in phonation quality between the treatment and control groups during evaluations. ...
The vocal cord in humans is essential in producing voice used in communication and interaction between us. Vocal cord paralysis causes dysphonia, which interferes with communication, causing disruptions towards social activity and daily activities. One of the managements for vocal cord paralysis is medialisation and augmentation of the vocal cord through injection laryngoplasty. Autologous fat is one of the best fillers used in this procedure, but it is highly absorbable and can be reabsorbed very quickly when injected into body tissues. Platelet Rich Fibrin (PRF) is a biomaterial consisting of growth factors that are thought to improve fat tissue viability by increasing adipogenesis and angiogenesis. Improvement in fat viability will improve clinical outcomes after the laryngoplasty procedure, potentially reducing the number of repeated injections needed to achieve a satisfactory resolution to vocal cord paralysis. The study evaluates a combination of PRF and autologous microlobular fat compared with autologous microlobular fat alone on laryngoplasty. This single-blinded randomised control trial recruit a total of 18 patients, which are then randomised into the treatment and control groups. The evaluation was done via computerised acoustic analysis/Multidimensional Voice Program (MDVP) parameters and maximum phonation time. The MDVP results and maximum phonation time in both groups showed clinical improvement after the operation with no statistically significant differences.
... The ECM of skeletal muscle is organized into the endomysium, perimysium and epimysium layers, which contain collagen I and III. The basal and reticular lamina are composed mainly of collagen fibrils (types I, III, IV and VI), laminin and fibronectin in a proteoglycan-rich gel (Dunn et al. 2018). The amniotic membrane (AM) can act as a scaffold with a template of the ECM. ...
Despite the high regenerative capacity of skeletal muscle, volumetric muscle loss (VML) is an irrecoverable injury. One therapeutic approach is the implantation of engineered biologic scaffolds enriched with stem cells. The objective of this study is to investigate the synergistic effect of high-intensity interval training (HIIT) and stem cell transplantation with an amniotic membrane scaffold on innervation, vascularization and muscle function after VML injury. A VML injury was surgically created in the tibialis anterior (TA) muscle in rats. The animals were randomly assigned to three groups: untreated negative control group (untreated), decellularized human amniotic membrane bio-scaffold group (dHAM) and dHAM seeded with adipose-derived stem cells, which differentiate into skeletal muscle cells (dHAM-ADSCs). Then, each group was divided into sedentary and HIIT subgroups. The exercise training protocol consisted of treadmill running for 8 weeks. The animals underwent in vivo functional muscle tests to evaluate maximal isometric contractile force. Regenerated TA muscles were harvested for molecular analyses and explanted tissues were analyzed with histological methods. The main finding was that HIIT promoted muscle regeneration, innervation and vascularization in regenerated areas in HIIT treatment subgroups, especially in the dHAM-ADSC subgroup. In parallel with innervation, maximal isometric force also increased in vivo. HIIT upregulated neurotrophic factor gene expression in skeletal muscle. The amniotic membrane bio-scaffold seeded with differentiated ADSC, in conjunction with exercise training, improved vascular perfusion and innervation and enhanced the functional and morphological healing process after VML injury. The implications of these findings are of potential importance for future efforts to develop engineered biological scaffolds and for the use of interval training programs in rehabilitation after VML injury.
... On the other hand, tissue ECM modification can also be a natural process. For instance, normal stem cells may modify their surrounding ECM for better biological functions [11][12][13][14]. Interestingly, it was shown that normalizing tumor ECM environment was able to "revert" cancer cell neoplastic phenotype [15] and limit tumor growth and dissemination [16], highlighting the essential role of ECM physicochemical properties on cancer development. ...
Background:
Breast cancer cells invading the connective tissues outside the mammary lobule or duct immerse in a reservoir of extracellular matrix (ECM) that is structurally and biochemically distinct from that of their site of origin. The ECM is a spatial network of matrix proteins, which not only provide physical support but also serve as bioactive ligands to the cells. It becomes evident that the dimensional, mechanical, structural, and biochemical properties of ECM are all essential mediators of many cellular functions. To better understand breast cancer development and cancer cell biology in native tissue environment, various tissue-mimicking culture models such as hydrogel have been developed. Collagen I (Col I) and Matrigel are the most common hydrogels used in cancer research and have opened opportunities for addressing biological questions beyond the two-dimensional (2D) cell cultures. Yet, it remains unclear whether these broadly used hydrogels can recapitulate the environmental properties of tissue ECM, and whether breast cancer cells grown on CoI I or Matrigel display similar phenotypes as they would on their native ECM.
Methods:
We investigated mammary epithelial cell phenotypes and metabolic profiles on animal breast ECM-derived tissue matrix gel (TMG), Col I, and Matrigel. Atomic force microscopy (AFM), fluorescence microscopy, acini formation assay, differentiation experiments, spatial migration/invasion assays, proliferation assay, and nuclear magnetic resonance (NMR) spectroscopy were used to examine biological phenotypes and metabolic changes. Student's t test was applied for statistical analyses.
Results:
Our data showed that under a similar physiological stiffness, the three types of hydrogels exhibited distinct microstructures. Breast cancer cells grown on TMG displayed quite different morphologies, surface receptor expression, differentiation status, migration and invasion, and metabolic profiles compared to those cultured on Col I and Matrigel. Depleting lactate produced by glycolytic metabolism of cancer cells abolished the cell proliferation promoted by the non-tissue-specific hydrogel.
Conclusion:
The full ECM protein-based hydrogel system may serve as a biologically relevant model system to study tissue- and disease-specific pathological questions. This work provides insights into tissue matrix regulation of cancer cell biomarker expression and identification of novel therapeutic targets for the treatment of human cancers based on tissue-specific disease modeling.
... The ECM is composed of specialized layers characterized by a variable composition of proteins, proteoglycans, and glycoproteins playing an integral role in structural support, force transmission, and regulation of the stem cell niche [46,106]. Thus, different collagen types can be labelled to evaluate the matrix composition and can be used as markers of connective tissue deposition. ...
... Thus, different collagen types can be labelled to evaluate the matrix composition and can be used as markers of connective tissue deposition. Indeed, although collagen I is the predominant type in the perimysium, the basement membrane is mainly comprised of laminin and collagen IV [47,48], whereas collagen I, III, and VI along with fibronectin in a proteoglycan-rich gel constitute the reticular lamina below the basement membrane (Table 1) [46][47][48][49][50]. The use of quantitative and qualitative high-magnification electron microscopy allowed the detailed description of the structure and composition of wild-type and fibrotic ECM. ...
Despite a massive body of knowledge which has been produced related to the mechanisms guiding muscle regeneration, great interest still moves the scientific community toward the study of different aspects of skeletal muscle homeostasis, plasticity, and regeneration. Indeed, the lack of effective therapies for several physiopathologic conditions suggests that a comprehensive knowledge of the different aspects of cellular behavior and molecular pathways, regulating each regenerative stage, has to be still devised. Hence, it is important to perform even more focused studies, taking the advantage of robust markers, reliable techniques, and reproducible protocols. Here, we provide an overview about the general aspects of muscle regeneration and discuss the different approaches to study the interrelated and time-dependent phases of muscle healing.
... The use of Biological MEM has been used as scaffold after the process of declellurization for repair of skeletal muscle defect. It has been proven that this scaffold influence stem cell activity within the MEM [36]. On parallel to that Aulino et al 2015, have proved that MEM of muscular tissue was able to cellularized with bone cells in situ and thus ECM offered great guide for cell migration from different mesenchymal tissues [37]. ...
... In summary, our results showed that MEM was an innovative reagent that could be used as a scaffold in reconstructive surgeries of the maxillofacial region. Only one study has demonstrated the osteogenic potential of MEM in the craniofacial region, particularly the mandible, in an animal model [36]. Nevertheless, to the best of our knowledge, this is the first study to show the use of decellularized skeletal muscle grafts infused with induced MSCs and resorbable bioactive SCPC to augment bone defect repair in the maxillofacial region. ...
Background:
Regenerative medicine provides novel approaches for treating various conditions and enhancing bone regeneration. Tissue interconversion is governed not only by intercellular interaction but also by the effect of micro-environmental changes and inductive extracellular cues.
Aim and objectives:
A preliminary study was conducted on prepared muscular extracellular matrix (MEM), where its osteogenic potential and colonization by blood vessels were assessed. Subsequently, MEM treated with human bone marrow stromal cells (hBMSCs), bone cement, and bone morphogenic protein 7 (BMP-7) was used to study bone regeneration and augmentation in an animal model.
Material and methods:
MEM grafts were prepared using a well-established protocol. Subclones derived from immortalized hBMSCs (TERT-hBMSCs) were used for graft characterization. Osteoblast differentiation was assessed using alkaline phosphatase (ALP) assay and Alizarin Red S staining. Mineralization was quantified and histology was assessed for the induced MEM. In an in vivo experiment, a calvarial defect was prepared to receive treated MEM grafts in 10 male nude mice, and 5 other mice were used as controls. After 8 weeks of grafting, the regenerated tissues were assessed using microcomputed tomography (micro-CT) and histological analysis.
Results:
Clinically, cortical bone regeneration was observed to bridge the defects in the study and positive control groups. Qualitative assessment of the regenerated bone using micro-CT analysis reported thinner trabeculae than normal native bone, with a high degree of anisotropy. Histologically, the bone thickness in the study group was one and half times that of the non-operated bone. The quantitative histomorphometric assessment showed a high median bone percentage surface area of 80.2 ± 6.0% (range, 26.9-90.3%).
Conclusion:
This study confirms the in vivo osteogenic properties of hBMSC-treated MEM and suggests novel strategies for bone augmentation.
... The extracellular matrix (ECM) in skeletal muscle plays a vital role in force transmission as well as development, maintenance, and regulation of the stem cell niche. 1 An important component of the muscle ECM is collagen I (COL), the primary isoform of collagen, which is found in the perimysium. 2 The COL triple helix is a heterotrimeric protein with two identical a1(I) chains and one a2(I) chain and it usually imparts tensile strength in the ECM. 3 Pathological overexpression of collagen results in muscle fibrosis, which is known to hinder muscle regeneration in several models of disease, injury, and aging. 1,[4][5][6][7] Fibrotic tissue deposition is known to impair muscle regeneration by dysregulating proliferation and differentiation of satellite cells 4,8 as well as other muscle-resident stem cells. 8,9 Laminin (LM) is a heterotrimeric glycoprotein with three chains (a, b, and c) that is found in the basal lamina of the satellite cell niche. ...
Skeletal muscle has a remarkable regenerative capacity in response to mild injury. However, when muscle is severely injured, muscle regeneration is impaired due to the loss of muscle-resident stem cells, known as satellite cells. Fibrotic tissue, primarily comprising collagen I (COL), is deposited with this critical loss of muscle. In recent studies, supplementation of laminin (LM)-111 has been shown to improve skeletal muscle regeneration in several models of disease and injury. Additionally, electrical stimulation (E-stim) has been investigated as a possible rehabilitation therapy to improve muscle's functional recovery. This study investigated the role of E-stim and substrate in regulating myogenic response. C2C12 myoblasts were allowed to differentiate into myotubes on COL- and LM-coated polydimethylsiloxane molds. The myotubes were subjected to E-stim and compared with nonstimulated controls. While E-stim resulted in increased myogenic activity, irrespective of substrate, LM supported increased proliferation and uniform distribution of C2C12 myoblasts. In addition, C2C12 myoblasts cultured on LM showed higher Sirtuin 1, mammalian target of rapamycin, desmin, nitric oxide, and vascular endothelial growth factor expression. Taken together, these results suggest that an LM substrate is more conducive to myoblast growth and differentiation in response to E-stim in vitro.
... Promoting effective regeneration of skeletal muscle following trauma remains a key challenge in tissue engineering. There have been several attempts at utilizing decellularized scaffolds to repair and regenerate skeletal muscle following VML [47]. However, these scaffolds have not been able to support sufficient levels of satellite cell activity and undergo rapid degradation [33]. ...
... Looking forward, the defects created in VML injuries are large, empty, amorphous gaps in the muscle tissue. Promoting adequate proliferation of satellite cells and myogenic progenitors are one of the major challenges of VML repair [4,7,26,47]. Implantation of autologous satellite cells in vivo have proven inefficient due to low viability and survival post-implantation [65,66]. ...
Volumetric muscle loss (VML) is a loss of over ~10% of muscle mass that results in functional impairment. Although skeletal muscle possesses the ability to repair and regenerate itself following minor injuries, VML injuries are irrecoverable. Currently, there are no successful clinical therapies for the treatment of VML. Previous studies have treated VML defects with decellularized extracellular matrix (D-ECM) scaffolds derived from either pig urinary bladder or small intestinal submucosa. These therapies were unsuccessful due to the poor mechanical stability of D-ECM leading to quick degradation in vivo. To circumvent these issues, in this manuscript aligned nanofibers of D-ECM were created using electrospinning that mimicked native muscle architecture and provided topographical cues to primary satellite cells. Additionally, combining D-ECM with polycaprolactone (PCL) improved the tensile mechanical properties of the electrospun scaffold. In vitro testing shows that the electrospun scaffold with aligned nanofibers of PCL and D-ECM supports satellite cell growth, myogenic protein expression, and myokine production.
Cultivated crustacean meat (CCM) is a means to create highly valued shrimp, lobster, and crab products directly from stem cells, thus removing the need to farm or fish live animals. Conventional crustacean enterprises face increasing pressures in managing overfishing, pollution, and the warming climate, so CCM may provide a way to ensure sufficient supply as global demand for these products grows. To support the development of CCM, this review briefly details crustacean cell culture work to date, before addressing what is presently known about crustacean muscle development, particularly the molecular mechanisms involved, and how this might relate to recent work on cultivated meat production in vertebrate species. Recognizing the current lack of cell lines available to establish CCM cultures, we also consider primary stem cell sources that can be obtained non-lethally including tissues from limbs which are readily released and regrown, and putative stem cells in circulating hemolymph. Molecular approaches to inducing myogenic differentiation and immortalization of putative stem cells are also reviewed. Finally, we assess the current status of tools available to CCM researchers, particularly antibodies, and propose avenues to address existing shortfalls in order to see the field progress.
Collagen is an important macromolecule of extracellular matrix (ECM) in bones, teeth, and temporomandibular joints. Mesenchymal stem cells (MSCs) interact with the components of the ECM such as collagen, proteoglycans, glycosaminoglycans (GAGs), and several proteins on behalf of variable matrix elasticity and bioactive cues. Synthetic collagen-based biomaterials could be effective scaffolds for regenerative dentistry applications due to mimicking of host tissues’ ECM. These biomaterials are biocompatible, biodegradable, readily available, and non-toxic to cells whose capability promotes cellular response and wound healing in the craniofacial region. Collagen could incorporate other biomolecules to induce mineralization in calcified tissues such as bone and tooth. Moreover, the addition of these molecules or other polymers to collagen-based biomaterials could enhance mechanical properties, which is important in load-bearing areas such as the mandible. A literature review was performed via reliable internet database (mainly PubMed) based on MeSH keywords. This review first describes the properties of collagen as a key protein in the structure of hard tissues. Then, it introduces different types of collagens, the correlation between collagen and MSCs, and the methods used to modify collagen in regenerative dentistry including recent progression on the regeneration of periodontium, dentin-pulp complex, and temporomandibular joint by applying collagen. Besides, the prospects and challenges of collagen-based biomaterials in the craniofacial region pointes out.
This review identifies some key concepts of muscle regeneration, viewed from perspectives of classical and modern research. Early insights noted the pattern and sequence of regeneration across species was similar, regardless of the type of injury, and differed from epimorphic limb regeneration. While potential benefits of exercise for tissue repair was debated, regeneration was not presumed to deliver functional restoration, especially after ischemia–reperfusion injury; muscle could develop fibrosis and ectopic bone and fat. Standard protocols and tools were identified as necessary for tracking injury and outcomes. Current concepts vastly extend early insights. Myogenic regeneration occurs within the environment of muscle tissue. Intercellular cross-talk generates an interactive system of cellular networks that with the extracellular matrix and local, regional, and systemic influences, forms the larger gestalt of the satellite cell niche. Regenerative potential and adaptive plasticity are overlain by epigenetically regionalized responsiveness and contributions by myogenic, endothelial, and fibroadipogenic progenitors and inflammatory and metabolic processes. Muscle architecture is a living portrait of functional regulatory hierarchies, while cellular dynamics, physical activity, and muscle–tendon–bone biomechanics arbitrate regeneration. The scope of ongoing research—from molecules and exosomes to morphology and physiology—reveals compelling new concepts in muscle regeneration that will guide future discoveries for use in application to fitness, rehabilitation, and disease prevention and treatment.
