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Artykuły w czasopismach na temat „Muscle stem cell”

Autor: Grafiati

Data publikacji: 4 czerwca 2021

Data aktualizacji: 25 stycznia 2025

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Liu, Qi, Su Pan, Shijie Liu, Sui Zhang, James T. Willerson, James F. Martin, and Richard A. F. Dixon. "Suppressing Hippo signaling in the stem cell niche promotes skeletal muscle regeneration." Stem Cells 39, no. 6 (February 18, 2021): 737–49. http://dx.doi.org/10.1002/stem.3343.

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Abstract Lack of blood flow to the lower extremities in peripheral arterial disease causes oxygen and nutrient deprivation in ischemic skeletal muscles, leading to functional impairment. Treatment options for muscle regeneration in this scenario are lacking. Here, we selectively targeted the Hippo pathway in myofibers, which provide architectural support for muscle stem cell niches, to facilitate functional muscle recovery in ischemic extremities by promoting angiogenesis, neovascularization, and myogenesis. We knocked down the core Hippo pathway component, Salvador (SAV1), by using an adeno-associated virus 9 (AAV9) vector expressing a miR30-based triple short-hairpin RNA (shRNA), controlled by a muscle-specific promoter. In a mouse hindlimb-ischemia model, AAV9 SAV1 shRNA administration in ischemic muscles induced nuclear localization of the Hippo effector YAP, accelerated perfusion restoration, and increased exercise endurance. Intravascular lectin labeling of the vasculature revealed enhanced angiogenesis. Using 5-ethynyl-2′-deoxyuridine to label replicating cellular DNA in vivo, we found SAV1 knockdown concurrently increased paired box transcription factor Pax7+ muscle satellite cell and CD31+ endothelial cell proliferation in ischemic muscles. To further study Hippo suppression in skeletal muscle regeneration, we used a cardiotoxin-induced muscle damage model in adult (12-15 weeks old) and aged mice (26-month old). Two weeks after delivery of AAV9 SAV1 shRNA into injured muscles, the distribution of regenerative myofibers shifted toward a larger cross-sectional area and increased capillary density compared with mice receiving AAV9 control. Together, these findings suggest our approach may have clinical promise in regenerative therapy for leg ischemia and muscle injury.

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Wang, Shuaiyu, Bao Zhang, Gregory C. Addicks, Hui Zhang, Keir J. Menzies, and Hongbo Zhang. "Muscle Stem Cell Immunostaining." Current Protocols in Mouse Biology 8, no. 3 (August 14, 2018): e47. http://dx.doi.org/10.1002/cpmo.47.

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Yin, Hang, Feodor Price, and Michael A. Rudnicki. "Satellite Cells and the Muscle Stem Cell Niche." Physiological Reviews 93, no. 1 (January 2013): 23–67. http://dx.doi.org/10.1152/physrev.00043.2011.

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Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration.

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Kodaka, Yusaku, Gemachu Rabu, and Atsushi Asakura. "Skeletal Muscle Cell Induction from Pluripotent Stem Cells." Stem Cells International 2017 (2017): 1–16. http://dx.doi.org/10.1155/2017/1376151.

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Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD). Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

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Memczak, Sebastian, and Juan CI Belmonte. "Overcoming muscle stem cell aging." Current Opinion in Genetics & Development 83 (December 2023): 102127. http://dx.doi.org/10.1016/j.gde.2023.102127.

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Ishii, Kana, Nobuharu Suzuki, Yo Mabuchi, Naoki Ito, Naomi Kikura, So-ichiro Fukada, Hideyuki Okano, Shin'ichi Takeda, and Chihiro Akazawa. "Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation During Muscle Regeneration." STEM CELLS 33, no. 10 (June 28, 2015): 3017–27. http://dx.doi.org/10.1002/stem.2058.

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Torrente, Yuan, Jacques-P. Tremblay, Federica Pisati, Marzia Belicchi, Barbara Rossi, Manuela Sironi, Franco Fortunato, et al. "Intraarterial Injection of Muscle-Derived Cd34+Sca-1+ Stem Cells Restores Dystrophin in mdx Mice." Journal of Cell Biology 152, no. 2 (January 22, 2001): 335–48. http://dx.doi.org/10.1083/jcb.152.2.335.

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Duchenne muscular dystrophy is a lethal recessive disease characterized by widespread muscle damage throughout the body. This increases the difficulty of cell or gene therapy based on direct injections into muscles. One way to circumvent this obstacle would be to use circulating cells capable of homing to the sites of lesions. Here, we showed that stem cell antigen 1 (Sca-1), CD34 double-positive cells purified from the muscle tissues of newborn mice are multipotent in vitro and can undergo both myogenic and multimyeloid differentiation. These muscle-derived stem cells were isolated from newborn mice expressing the LacZ gene under the control of the muscle-specific desmin or troponin I promoter and injected into arterial circulation of the hindlimb of mdx mice. The ability of these cells to interact and firmly adhere to endothelium in mdx muscles microcirculation was demonstrated by intravital microscopy after an intraarterial injection. Donor Sca-1, CD34 muscle-derived stem cells were able to migrate from the circulation into host muscle tissues. Histochemical analysis showed colocalization of LacZ and dystrophin expression in all muscles of the injected hindlimb in all of five out of five 8-wk-old treated mdx mice. Their participation in the formation of muscle fibers was significantly increased by muscle damage done 48 h after their intraarterial injection, as indicated by the presence of 12% β-galactosidase–positive fibers in muscle cross sections. Normal dystrophin transcripts detected enzymes in the muscles of the hind limb injected intraarterially by the mdx reverse transcription polymerase chain reaction method, which differentiates between normal and mdx message. Our results showed that the muscle-derived stem cells first attach to the capillaries of the muscles and then participate in regeneration after muscle damage.

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Borok, Matthew, Nathalie Didier, Francesca Gattazzo, Teoman Ozturk, Aurelien Corneau, Helene Rouard, and Frederic Relaix. "Progressive and Coordinated Mobilization of the Skeletal Muscle Niche throughout Tissue Repair Revealed by Single-Cell Proteomic Analysis." Cells 10, no. 4 (March 28, 2021): 744. http://dx.doi.org/10.3390/cells10040744.

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Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.

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Wagers, Amy J. "Stem Cell Rejuvenation." Blood 124, no. 21 (December 6, 2014): SCI—42—SCI—42. http://dx.doi.org/10.1182/blood.v124.21.sci-42.sci-42.

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Effective functioning of the body’s tissues and organs depends upon innate regenerative processes that maintain proper cell numbers during homeostasis and replace damaged cells after injury. In many tissues, regenerative potential is determined by the presence and functionality of dedicated populations of stem and progenitor cells, which respond to exogenous cues to produce replacement cells when needed. Understanding how these unspecialized precursors are maintained and regulated is essential for understanding the fundamental biology of tissues. In addition, this knowledge has practical implications, as stem cell regenerative potential can be exploited therapeutically by transplantation to replenish the stem cell pool or by pharmacological manipulation to boost the repair activity of cells already present in the tissue. Ongoing work in my laboratory focuses on defining how changes in stem cell activity impact tissue regeneration throughout life, and identifying physiological and pathological signals that modulate regenerative function in an age-dependent manner. Our recent data using parabiosis and transplantation models suggests that the circulatory system serves as a major source of such signals. In particular, exposure of aged tissues, including skeletal muscle, cardiac muscle and neural cells, to a “youthful” systemic environment appears to reverse many indicators of age-related pathology and restores robust regeneration following injury. While prior studies have identified a handful of systemic “aging” factors, discovery of the humoral “rejuvenating” factors that act on tissue stem cells to restore regenerative function has been relatively more elusive. In recent work, we identified that the circulating hormone Growth Differentiation Factor 11 (GDF11) is a rejuvenating factor for skeletal muscle and other tissues. Supplementation of systemic GDF11 levels, which normally decline with age in mice and humans, was sufficient to restore stem cell function in the skeletal muscle and other tissues, and improved physical function in aged mice. Taken together, these data reveal critical mechanisms in the regulation of aging by blood-borne factors and identify a promising therapeutic target candidate for the reversal of age-related tissue and stem cell dysfunction. Disclosures No relevant conflicts of interest to declare.

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Heslop, L., J. E. Morgan, and T. A. Partridge. "Evidence for a myogenic stem cell that is exhausted in dystrophic muscle." Journal of Cell Science 113, no. 12 (June 15, 2000): 2299–308. http://dx.doi.org/10.1242/jcs.113.12.2299.

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Injection of the myotoxin notexin, was found to induce regeneration in muscles that had been subjected to 18 Gy of radiation. This finding was unexpected as irradiation doses of this magnitude are known to block regeneration in dystrophic (mdx) mouse muscle. To investigate this phenomenon further we subjected mdx and normal (C57Bl/10) muscle to irradiation and notexin treatment and analysed them in two ways. First by counting the number of newly regenerated myofibres expressing developmental myosin in cryosections of damaged muscles. Second, by isolating single myofibres from treated muscles and counting the number of muscle precursor cells issuing from these over 2 day and 5 day periods. After irradiation neither normal nor dystrophic muscles regenerate to any significant extent. Moreover, single myofibres cultured from such muscles produce very few muscle precursor cells and these undergo little or no proliferation. However, when irradiated normal and mdx muscles were subsequently treated with notexin, regeneration was observed. In addition, some of the single myofibres produced rapidly proliferative muscle precursor cells when cultured. This occurred more frequently, and the myogenic cells proliferated more extensively, with fibres cultured from normal compared with dystrophic muscles. Even after 25 Gy, notexin induced some regeneration but no proliferative myogenic cells remained associated with the muscle fibres. Thus, skeletal muscles contain a number of functionally distinct populations of myogenic cells. Most are radiation sensitive. However, some survive 18 Gy as proliferative myogenic cells that can be evoked by extreme conditions of muscle damage; this population is markedly diminished in muscles of the mdx mouse. A small third population survives 25 Gy and forms muscle but not proliferative myogenic cells.

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Zammit, Peter S., and Jonathan R. Beauchamp. "The skeletal muscle satellite cell: stem cell or son of stem cell?" Differentiation 68, no. 4-5 (October 2001): 193–204. http://dx.doi.org/10.1046/j.1432-0436.2001.680407.x.

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de Morree, Antoine, Julian D. D. Klein, Qiang Gan, Jean Farup, Andoni Urtasun, Abhijnya Kanugovi, Biter Bilen, Cindy T. J. van Velthoven, Marco Quarta, and Thomas A. Rando. "Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function." Science 366, no. 6466 (November 7, 2019): 734–38. http://dx.doi.org/10.1126/science.aax1694.

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Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

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Tchao, Jason, Jong Jin Kim, Bo Lin, Guy Salama, Cecilia W. Lo, Lei Yang, and Kimimasa Tobita. "Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells." International Journal of Tissue Engineering 2013 (December 5, 2013): 1–15. http://dx.doi.org/10.1155/2013/198762.

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During development, cardiac and skeletal muscle share major transcription factors and sarcomere proteins which were generally regarded as specific to either cardiac or skeletal muscle but not both in terminally differentiated adult cardiac or skeletal muscle. Here, we investigated whether artificial muscle constructed from human skeletal muscle derived stem cells (MDSCs) recapitulates developmental similarities between cardiac and skeletal muscle. We constructed 3-dimensional collagen-based engineered muscle tissue (EMT) using MDSCs (MDSC-EMT) and compared the biochemical and contractile properties with EMT using induced pluripotent stem (iPS) cell-derived cardiac cells (iPS-EMT). Both MDSC-EMT and iPS-EMT expressed cardiac specific troponins, fast skeletal muscle myosin heavy chain, and connexin-43 mimicking developing cardiac or skeletal muscle. At the transcriptional level, MDSC-EMT and iPS-EMT upregulated both cardiac and skeletal muscle-specific genes and expressed Nkx2.5 and Myo-D proteins. MDSC-EMT displayed intracellular calcium ion transients and responses to isoproterenol. Contractile force measurements of MDSC-EMT demonstrated functional properties of immature cardiac and skeletal muscle in both tissues. Results suggest that the EMT from MDSCs mimics developing cardiac and skeletal muscle and can serve as a useful in vitro functioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair.

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Camps, Jordi, Hanne Grosemans, Rik Gijsbers, Christa Maes, and Maurilio Sampaolesi. "Growth Factor Screening in Dystrophic Muscles Reveals PDGFB/PDGFRB-Mediated Migration of Interstitial Stem Cells." International Journal of Molecular Sciences 20, no. 5 (March 5, 2019): 1118. http://dx.doi.org/10.3390/ijms20051118.

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Progressive muscle degeneration followed by dilated cardiomyopathy is a hallmark of muscular dystrophy. Stem cell therapy is suggested to replace diseased myofibers by healthy myofibers, although so far, we are faced by low efficiencies of migration and engraftment of stem cells. Chemokines are signalling proteins guiding cell migration and have been shown to tightly regulate muscle tissue repair. We sought to determine which chemokines are expressed in dystrophic muscles undergoing tissue remodelling. Therefore, we analysed the expression of chemokines and chemokine receptors in skeletal and cardiac muscles from Sarcoglycan-α null, Sarcoglycan-β null and immunodeficient Sgcβ-null mice. We found that several chemokines are dysregulated in dystrophic muscles. We further show that one of these, platelet-derived growth factor-B, promotes interstitial stem cell migration. This finding provides perspective to an approachable mechanism for improving stem cell homing towards dystrophic muscles.

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Fujimaki, Shin, Tamami Wakabayashi, Tohru Takemasa, Makoto Asashima, and Tomoko Kuwabara. "Diabetes and Stem Cell Function." BioMed Research International 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/592915.

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Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer’s disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment.

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Liang, Yu, Hui Han, Qiuchan Xiong, Chunlong Yang, Lu Wang, Jieyi Ma, Shuibin Lin, and Yi-Zhou Jiang. "METTL3-Mediated m6A Methylation Regulates Muscle Stem Cells and Muscle Regeneration by Notch Signaling Pathway." Stem Cells International 2021 (May 14, 2021): 1–13. http://dx.doi.org/10.1155/2021/9955691.

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The Pax7+ muscle stem cells (MuSCs) are essential for skeletal muscle homeostasis and muscle regeneration upon injury, while the molecular mechanisms underlying muscle stem cell fate determination and muscle regeneration are still not fully understood. N6-methyladenosine (m6A) RNA modification is catalyzed by METTL3 and plays important functions in posttranscriptional gene expression regulation and various biological processes. Here, we generated muscle stem cell-specific METTL3 conditional knockout mouse model and revealed that METTL3 knockout in muscle stem cells significantly inhibits the proliferation of muscle stem cells and blocks the muscle regeneration after injury. Moreover, knockin of METTL3 in muscle stem cells promotes the muscle stem cell proliferation and muscle regeneration in vivo. Mechanistically, METTL3-m6A-YTHDF1 axis regulates the mRNA translation of Notch signaling pathway. Our data demonstrated the important in vivo physiological function of METTL3-mediated m6A modification in muscle stem cells and muscle regeneration, providing molecular basis for the therapy of stem cell-related muscle diseases.

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Tedesco, Francesco S., and Giulio Cossu. "Stem cell therapies for muscle disorders." Current Opinion in Neurology 25, no. 5 (October 2012): 597–603. http://dx.doi.org/10.1097/wco.0b013e328357f288.

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Hammond, H. Kirk. "Skeletal Muscle-Derived Stem Cell Transplantation." Journal of the American College of Cardiology 50, no. 17 (October 2007): 1685–87. http://dx.doi.org/10.1016/j.jacc.2007.07.027.

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Le Bot, Nathalie. "Aged muscle drives stem cell demise." Nature Cell Biology 14, no. 11 (November 2012): 1129. http://dx.doi.org/10.1038/ncb2625.

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Saber, John, Alexander Y. T. Lin, and Michael A. Rudnicki. "Single-cell analyses uncover granularity of muscle stem cells." F1000Research 9 (January 21, 2020): 31. http://dx.doi.org/10.12688/f1000research.20856.1.

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Satellite cells are the main muscle-resident cells responsible for muscle regeneration. Much research has described this population as being heterogeneous, but little is known about the different roles each subpopulation plays. Recent advances in the field have utilized the power of single-cell analysis to better describe and functionally characterize subpopulations of satellite cells as well as other cell groups comprising the muscle tissue. Furthermore, emerging technologies are opening the door to answering as-yet-unresolved questions pertaining to satellite cell heterogeneity and cell fate decisions.

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Esper, Greyson Vitor Zanatta, Graciela Conceição Pignatari, Marcio Nogueira Rodrigues, Heloisa Godoi Bertagnon, Isabella Rodrigues Fernandes, Nanci Nascimento, Angela Maria Florencio Tabosa, Patrícia Cristina Baleeiro Beltrão-Braga, and Maria Angelica Miglino. "Aquapuncture Using Stem Cell Therapy to Treat Mdx Mice." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/132706.

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Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to absence or decrease of dystrophin protein generating progressive muscle degeneration. Cell therapy using mesenchymal stem cell (MSC) has been described as a treatment to DMD. In this work, MSC derived from deciduous teeth, called stem cells from human exfoliated deciduous teeth (SHED), were injected in acupoint as an alternative therapy to minimize muscle degeneration in twenty-two mdx mice. The treatment occurred three times with intervals of 21 days, and animals were analyzed four times: seven days prior treatment (T-7); 10 days after first treatment (T10); 10 days after second treatment (T31); and 10 days after third treatment (T52). Animals were evaluated by wire test for estimate strength and blood was collected to perform a creatinine phosphokinase analysis. After euthanasia, cranial tibial muscles were collected and submitted to histological and immunohistochemistry analyses. Treated groups presented improvement of strength and reduced creatinine phosphokinase levels. Also, a slight dystrophin increase was observed in tibial cranial muscle when aquapuncture was associated SHED. All therapies have minimized muscle degeneration, but the association of aquapuncture with SHED appears to have better effect, reducing muscle damage, suggesting a therapeutic value.

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Sleep, Eduard, Benjamin D. Cosgrove, Mark T. McClendon, Adam T. Preslar, Charlotte H. Chen, M. Hussain Sangji, Charles M. Rubert Pérez, et al. "Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation." Proceedings of the National Academy of Sciences 114, no. 38 (September 5, 2017): E7919—E7928. http://dx.doi.org/10.1073/pnas.1708142114.

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Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice.

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Siegel, Ashley L., Kevin Atchison, Kevin E. Fisher, George E. Davis, and D. D. W. Cornelison. "3D Timelapse Analysis of Muscle Satellite Cell Motility." Stem Cells 27, no. 10 (October 2009): 2527–38. http://dx.doi.org/10.1002/stem.178.

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Tierney, Matthew, Christina Garcia, Matthew Bancone, Alessandra Sacco, and Kirkwood E. Personius. "Innervation of dystrophic muscle after muscle stem cell therapy." Muscle & Nerve 54, no. 4 (August 17, 2016): 763–68. http://dx.doi.org/10.1002/mus.25115.

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Baek, Jieun, Bokyeong Ryu, Jin Kim, Seul-Gi Lee, Min-Seok Oh, Ki-Sung Hong, Eun-Young Kim, C.-Yoon Kim, and Hyung-Min Chung. "Immunomodulation of Pluripotent Stem Cell-Derived Mesenchymal Stem Cells in Rotator Cuff Tears Model." Biomedicines 10, no. 7 (June 29, 2022): 1549. http://dx.doi.org/10.3390/biomedicines10071549.

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Background: Rotator cuff tears (RCTs) induce chronic muscle weakness and shoulder pain. Treatment of RCT using surgery or drugs causes lipid infiltration and fibrosis, which hampers tissue regeneration and complete recovery. The pluripotent stem cell-derived multipotent mesenchymal stem cells (M-MSCs) represent potential candidate next-generation therapies for RCT. Methods: The difference between M-MSCs and adult-MSCs was compared and analyzed using next-generation sequencing (NGS). In addition, using a rat model of RCT, the muscle recovery ability of M-MSCs and adult-MSCs was evaluated by conducting a histological analysis and monitoring the cytokine expression level. Results: Using NGS, it was confirmed that M-MSC was suitable for transplantation because of its excellent ability to regulate inflammation that promotes tissue repair and reduced apoptosis and rejection during transplantation. In addition, while M-MSCs persisted for up to 8 weeks in vivo, they significantly reduced inflammation and adipogenesis-related cytokine levels in rat muscle. Significant differences were also confirmed in histopathological remission. Conclusions: M-MSCs remain in the body longer to modulate immune responses in RCTs and have a greater potential to improve muscle recovery by alleviating acute inflammatory responses. This indicates that M-MSCs could be used in potential next-generation RCT therapies.

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Zhao, Shudong, Jishizhan Chen, Lei Wu, Xin Tao, Naheem Yaqub, and Jinke Chang. "Induced Pluripotent Stem Cells for Tissue-Engineered Skeletal Muscles." International Journal of Molecular Sciences 24, no. 14 (July 15, 2023): 11520. http://dx.doi.org/10.3390/ijms241411520.

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Skeletal muscle, which comprises a significant portion of the body, is responsible for vital functions such as movement, metabolism, and overall health. However, severe injuries often result in volumetric muscle loss (VML) and compromise the regenerative capacity of the muscle. Tissue-engineered muscles offer a potential solution to address lost or damaged muscle tissue, thereby restoring muscle function and improving patients’ quality of life. Induced pluripotent stem cells (iPSCs) have emerged as a valuable cell source for muscle tissue engineering due to their pluripotency and self-renewal capacity, enabling the construction of tissue-engineered artificial skeletal muscles with applications in transplantation, disease modelling, and bio-hybrid robots. Next-generation iPSC-based models have the potential to revolutionize drug discovery by offering personalized muscle cells for testing, reducing reliance on animal models. This review provides a comprehensive overview of iPSCs in tissue-engineered artificial skeletal muscles, highlighting the advancements, applications, advantages, and challenges for clinical translation. We also discussed overcoming limitations and considerations in differentiation protocols, characterization methods, large-scale production, and translational regulations. By tackling these challenges, iPSCs can unlock transformative advancements in muscle tissue engineering and therapeutic interventions for the future.

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Haond, Celine, Francoise Farace, Martine Guillier, Yann Lecluse, Ludmilla Mecaj, Frederic Mazurier, William Vainchenker, and Ali G. Turhan. "Comparative Single Cell Analysis of Side Population (SP) / CD45+ Cells from Marrow and Skeletal Muscle Reveals Evidence of Genuine Stem Cell Function and Multilineage Differentiation Ability in Muscle-Resident Stem Cells." Blood 104, no. 11 (November 16, 2004): 2688. http://dx.doi.org/10.1182/blood.v104.11.2688.2688.

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Abstract Murine skeletal muscle harbors hematopoietic stem cells. It has been suggested that these cells of hematopoietic origin have an altered stem cell function possibly due to their inadeqaute environment as compared to marrow-resident stem cells. The comparative quantitative and qualitative analysis of marrow and muscle-resident stem cells at the single cell level has not been performed so far. To this end, we have performed in vitro and in vivo stem cell detection assays using highly purified CD45+ cells, side population (SP) cells and SP/CD45 +cells. Muscle and marrow were found to contain 1–3 % and 0.2– 0.5 % of SP cells, respectively. The frequency of SP/CD45+ phenotype was 0.1–0.4% for the marrow and 0.2–0.5% in the muscle. Hematopoietic clonogenic cell efficiency from total nucleated cells was 1/500 for marrow and 1/10000 for muscle. Clonogenic efficiency of muscle CD45+ cells was about 1/3rd of that of marrow but with preserved erythroid and granulocytic differentiation ability. The use of SP/CD45+ cells from both muscle and marrow allowed an enrichment of clonogenic capacity by 60-fold in marrow and 360-fold in the muscle. In limiting dilution assays performed in MS-5 cells over 5 weeks, LTC-IC frequency was found to be 1/100 for marrow SP/CD45+ cells and 1/550 for muscle SP/CD45+ cells. To determine cloning and differentiation abilities of single SP/CD45+ cells purified from muscle and marrow, we have cultured single FACS-sorted cells in the presence of SCF, l-Flt3, IL-7, IL-11 and / or the OP-9 stroma (which promotes hematopoietic cell differentiation from embryonic stem cells) for 14– 21 days. Single SP/CD45+ cell cloning efficiency was 14% for marrow (109 wells + / 768) and 3% for muscle (42 wells+ / 1248). Despite this difference, single muscle-derived SP/CD45+ cells exhibited very robust proliferative activity, with 8– 13 cell doubling being obtained in 8 days in the presence of either cytokines alone or OP9 cells + cytokines, leading to absolute numbers of up to 60000/well. More importantly, like marrow SP/CD45+ cells, individual muscle-derived cells exhibited multilineage differentiation ability, with evidence of myeloid, B, NK and dendritic cell differentiation at day 14–21. In in vivo reconstitution experiments, the mean % of Ly5.1 chimerism generated after transplantation of of highly purified marrow SP/CD45+ cells ( 30 – 5700 cells/mouse, n=25 mice) and muscle SP/CD45+ cells ( 300–6500 cells / mouse) was 60% and 9 %, respectively (+ 8 months). To determine if this difference could be due to homing characteristics, SP+/CD45+ cells of marrow (300 /mouse) and muscle origin (300–500/mouse) were transplanted in lethally irradiated Ly5.2 mice by intrafemoral injection. In these assays, muscle-derived SP+/CD45+ cells gave rise also to persistent but lower Ly5.1 chimerisms as compared to marrow (+ 3 months). Thus, our results demonstrate that murine skeletal muscle harbors true stem cells with extensive proliferative and multilineage differentiation ability but as compared to marrow this population occurs with lower frequency. This heterogeneity, explaining an apparently reduced stem cell function in vivo, is not due to homing inability. Experiments underway will determine the in vivo potential of single muscle-resident stem cells.

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Gopinath, Suchitra D., and Thomas A. Rando. "Stem Cell Review Series: Aging of the skeletal muscle stem cell niche." Aging Cell 7, no. 4 (August 2008): 590–98. http://dx.doi.org/10.1111/j.1474-9726.2008.00399.x.

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Hashimoto, N. "Muscle reconstitution by muscle satellite cell descendants with stem cell-like properties." Development 131, no. 21 (November 1, 2004): 5481–90. http://dx.doi.org/10.1242/dev.01395.

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Forcina, Laura, Carmen Miano, Laura Pelosi, and Antonio Musarò. "An Overview About the Biology of Skeletal Muscle Satellite Cells." Current Genomics 20, no. 1 (February 27, 2019): 24–37. http://dx.doi.org/10.2174/1389202920666190116094736.

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The peculiar ability of skeletal muscle tissue to operate adaptive changes during post-natal development and adulthood has been associated with the existence of adult somatic stem cells. Satellite cells, occupying an exclusive niche within the adult muscle tissue, are considered bona fide stem cells with both stem-like properties and myogenic activities. Indeed, satellite cells retain the capability to both maintain the quiescence in uninjured muscles and to be promptly activated in response to growth or regenerative signals, re-engaging the cell cycle. Activated cells can undergo myogenic differentiation or self-renewal moving back to the quiescent state. Satellite cells behavior and their fate decision are finely controlled by mechanisms involving both cell-autonomous and external stimuli. Alterations in these regulatory networks profoundly affect muscle homeostasis and the dynamic response to tissue damage, contributing to the decline of skeletal muscle that occurs under physio-pathologic conditions. Although the clear myogenic activity of satellite cells has been described and their pivotal role in muscle growth and regeneration has been reported, a comprehensive picture of inter-related mechanisms guiding muscle stem cell activity has still to be defined. Here, we reviewed the main regulatory networks determining satellite cell behavior. In particular, we focused on genetic and epigenetic mechanisms underlining satellite cell maintenance and commitment. Besides intrinsic regulations, we reported current evidences about the influence of environmental stimuli, derived from other cell populations within muscle tissue, on satellite cell biology.

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Garg, Koyal, and Marni D. Boppart. "Influence of exercise and aging on extracellular matrix composition in the skeletal muscle stem cell niche." Journal of Applied Physiology 121, no. 5 (November 1, 2016): 1053–58. http://dx.doi.org/10.1152/japplphysiol.00594.2016.

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Skeletal muscle is endowed with a remarkable capacity for regeneration, primarily due to the reserve pool of muscle resident satellite cells. The satellite cell is the physiologically quiescent muscle stem cell that resides beneath the basal lamina and adjacent to the sarcolemma. The anatomic location of satellite cells is in close proximity to vasculature where they interact with other muscle resident stem/stromal cells (e.g., mesenchymal stem cells and pericytes) through paracrine mechanisms. This mini-review describes the components of the muscle stem cell niche, as well as the influence of exercise and aging on the muscle stem cell niche. Although exercise promotes ECM reorganization and stem cell accumulation, aging is associated with dense ECM deposition and loss of stem cell function resulting in reduced regenerative capacity and strength. An improved understanding of the niche elements will be valuable to inform the development of therapeutic interventions aimed at improving skeletal muscle regeneration and adaptation over the life span.

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Ūsas, Arvydas, Justinas Mačiulaitis, Romaldas Mačiulaitis, Neli Jakubonienė, Arvydas Milašius, and Johnny Huard. "Skeletal Muscle-Derived Stem Cells: Implications for Cell-Mediated Therapies." Medicina 47, no. 9 (October 5, 2011): 469. http://dx.doi.org/10.3390/medicina47090068.

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Current advances in stem cell research and innovative biological approaches in the field of tissue engineering and regenerative medicine could eventually translate into prospective clinical applications. Various adult organs and tissues harbor stem and progenitor cells that could potentially be used to repair, regenerate, and restore a variety of different tissues following acute injury or tissue destructive diseases. Skeletal muscle is a very convenient and plentiful source of somatic stem cells. It contains several distinct populations of myogenic stem cells including satellite cells that are mainly responsible for muscle growth and regeneration, and multipotent muscle-derived stem cells (MDSCs). Although both cell populations share some phenotypic similarities, MDSCs display a much greater differentiation potential in vitro and are capable of regenerating various tissues in vivo. Furthermore, these cells not only participate in the regeneration process by differentiating into tissue-specific cell types, but also promote endogenous tissue repair by secreting a multitude of trophic factors. In this article, we describe the biological aspects of MDSC isolation and characterization and provide an overview of potential therapeutic application of these cells for the treatment of cardiac and skeletal muscle injuries and diseases, urological dysfunction, and bone and cartilage defects. We also discuss major challenges and limitations currently faced by MDSC-based therapies that await resolution before these techniques can be applied clinically.

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Challa, Stalin Reddy, and Swathi Goli. "Differentiation of Human Embryonic Stem Cells into Engrafting Myogenic Precursor Cells." Stem cell Research and Therapeutics International 1, no. 1 (April 16, 2019): 01–05. http://dx.doi.org/10.31579/2643-1912/002.

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Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.

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Parisi, Alice, Floriane Lacour, Lorenzo Giordani, Sabine Colnot, Pascal Maire, and Fabien Le Grand. "APC is required for muscle stem cell proliferation and skeletal muscle tissue repair." Journal of Cell Biology 210, no. 5 (August 24, 2015): 717–26. http://dx.doi.org/10.1083/jcb.201501053.

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The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.

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Fujimaki, Shin, Masanao Machida, Ryo Hidaka, Makoto Asashima, Tohru Takemasa, and Tomoko Kuwabara. "Intrinsic Ability of Adult Stem Cell in Skeletal Muscle: An Effective and Replenishable Resource to the Establishment of Pluripotent Stem Cells." Stem Cells International 2013 (2013): 1–18. http://dx.doi.org/10.1155/2013/420164.

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Adult stem cells play an essential role in mammalian organ maintenance and repair throughout adulthood since they ensure that organs retain their ability to regenerate. The choice of cell fate by adult stem cells for cellular proliferation, self-renewal, and differentiation into multiple lineages is critically important for the homeostasis and biological function of individual organs. Responses of stem cells to stress, injury, or environmental change are precisely regulated by intercellular and intracellular signaling networks, and these molecular events cooperatively define the ability of stem cell throughout life. Skeletal muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle contains myogenic satellite cells and muscle-derived stem cells that retain multipotent differentiation abilities. These stem cell populations have the capacity for long-term proliferation and high self-renewal. The molecular mechanisms associated with deficits in skeletal muscle and stem cell function have been extensively studied. Muscle-derived stem cells are an obvious, readily available cell resource that offers promise for cell-based therapy and various applications in the field of tissue engineering. This review describes the strategies commonly used to identify and functionally characterize adult stem cells, focusing especially on satellite cells, and discusses their potential applications.

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Torrente, Yvan, Geoffrey Camirand, Federica Pisati, Marzia Belicchi, Barbara Rossi, Fabio Colombo, Mosthapha El Fahime, et al. "Identification of a putative pathway for the muscle homing of stem cells in a muscular dystrophy model." Journal of Cell Biology 162, no. 3 (July 28, 2003): 511–20. http://dx.doi.org/10.1083/jcb.200210006.

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Attempts to repair muscle damage in Duchenne muscular dystrophy (DMD) by transplanting skeletal myoblasts directly into muscles are faced with the problem of the limited migration of these cells in the muscles. The delivery of myogenic stem cells to the sites of muscle lesions via the systemic circulation is a potential alternative approach to treat this disease. Muscle-derived stem cells (MDSCs) were obtained by a MACS® multisort method. Clones of MDSCs, which were Sca-1+/CD34−/L-selectin+, were found to adhere firmly to the endothelium of mdx dystrophic muscles after i.v. or i.m. injections. The subpopulation of Sca-1+/CD34− MDSCs expressing L-selectin was called homing MDSCs (HMDSCs). Treatment of HMDSCs with antibodies against L-selectin prevented adhesion to the muscle endothelium. Importantly, we found that vascular endothelium from striate muscle of young mdx mice expresses mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a ligand for L-selectin. Our results showed for the first time that the expression of the adhesion molecule L-selectin is important for muscle homing of MDSCs. This discovery will aid in the improvement of a potential therapy for muscular dystrophy based on the systemic delivery of MDSCs.

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Stephenson, Makeda, Daniel H. Reich, and Kenneth R. Boheler. "Induced pluripotent stem cell-derived vascular smooth muscle cells." Vascular Biology 2, no. 1 (January 9, 2020): R1—R15. http://dx.doi.org/10.1530/vb-19-0028.

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The reproducible generation of human-induced pluripotent stem cell (hiPSC)-derived vascular smooth muscle cells (vSMCs) in vitro has been critical to overcoming many limitations of animal and primary cell models of vascular biology and disease. Since this initial advance, research in the field has turned toward recapitulating the naturally occurring subtype specificity found in vSMCs throughout the body, and honing functional models of vascular disease. In this review, we summarize vSMC derivation approaches, including current phenotype and developmental origin-specific methods, and applications of vSMCs in functional disease models and engineered tissues. Further, we discuss the challenges of heterogeneity in hiPSC-derived tissues and propose approaches to identify and isolate vSMC subtype populations.

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Englund, Davis A., Bailey D. Peck, Kevin A. Murach, Ally C. Neal, Hannah A. Caldwell, John J. McCarthy, Charlotte A. Peterson, and Esther E. Dupont-Versteegden. "Resident muscle stem cells are not required for testosterone-induced skeletal muscle hypertrophy." American Journal of Physiology-Cell Physiology 317, no. 4 (October 1, 2019): C719—C724. http://dx.doi.org/10.1152/ajpcell.00260.2019.

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It is postulated that testosterone-induced skeletal muscle hypertrophy is driven by myonuclear accretion as the result of satellite cell fusion. To directly test this hypothesis, we utilized the Pax7-DTA mouse model to deplete satellite cells in skeletal muscle followed by testosterone administration. Pax7-DTA mice (6 mo of age) were treated for 5 days with either vehicle [satellite cell replete (SC+)] or tamoxifen [satellite cell depleted (SC-)]. Following a washout period, a testosterone propionate or sham pellet was implanted for 21 days. Testosterone administration caused a significant increase in muscle fiber cross-sectional area in SC+ and SC- mice in both oxidative (soleus) and glycolytic (plantaris and extensor digitorum longus) muscles. In SC+ mice treated with testosterone, there was a significant increase in both satellite cell abundance and myonuclei that was completely absent in testosterone-treated SC- mice. These findings provide direct evidence that testosterone-induced muscle fiber hypertrophy does not require an increase in satellite cell abundance or myonuclear accretion. Listen to a podcast about this Rapid Report with senior author E. E. Dupont-Versteegden ( https://ajpcell.podbean.com/e/podcast-on-paper-that-shows-testosterone-induced-skeletal-muscle-hypertrophy-does-not-need-muscle-stem-cells /).

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Lee, Jae-Hoon, Tae-Kyung Kim, Min-Cheol Kang, Minkyung Park, and Yun-Sang Choi. "Methods to Isolate Muscle Stem Cells for Cell-Based Cultured Meat Production: A Review." Animals 14, no. 5 (March 6, 2024): 819. http://dx.doi.org/10.3390/ani14050819.

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Cultured meat production relies on various cell types, including muscle stem cells (MuSCs), embryonic stem cell lines, induced pluripotent cell lines, and naturally immortalized cell lines. MuSCs possess superior muscle differentiation capabilities compared to the other three cell lines, making them key for cultured meat development. Therefore, to produce cultured meat using MuSCs, they must first be effectively separated from muscles. At present, the methods used to isolate MuSCs from muscles include (1) the pre-plating method, using the ability of cells to adhere differently, which is a biological characteristic of MuSCs; (2) the density gradient centrifugation method, using the intrinsic density difference of cells, which is a physical characteristic of MuSCs; and (3) fluorescence- and magnetic-activated cell sorting methods, using the surface marker protein on the cell surface of MuSCs, which is a molecular characteristic of MuSCs. Further efficient and valuable methods for separating MuSCs are expected to be required as the cell-based cultured meat industry develops. Thus, we take a closer look at the four methods currently in use and discuss future development directions in this review.

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Shadrach, Jennifer L., and Amy J. Wagers. "Stem cells for skeletal muscle repair." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1575 (August 12, 2011): 2297–306. http://dx.doi.org/10.1098/rstb.2011.0027.

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Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.

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Čížková, Dana, Z. Komárková, A. Bezrouk, L. Macháčková, J. Vávrová, S. Filip, and J. Mokrý. "Bone Marrow-Derived Cells Participate in Composition of the Satellite Cell Niche in Intact and Regenerating Mouse Skeletal Muscle." Folia Biologica 64, no. 5 (2018): 155–66. http://dx.doi.org/10.14712/fb2018064050155.

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The cellular components of the satellite cell niche participate in the regulation of skeletal muscle regeneration. Beside myogenic cells at different developmental stages, this niche is formed by cells of the immune system, the interstitial connective tissue and the vascular system. Unambiguous determination of the origin of these cell types could contribute to optimization of the cell-based therapy of skeletal muscle disorders. In our work, we intravenously transplanted mouse GFP+ unseparated bone marrow cells into whole-body lethally irradiated immunocompetent mice four weeks before cardiotoxin-induced injury of the recipients’ skeletal muscles. Seven and 28 days after the toxin injection, the injured regenerating and contralateral intact muscles were examined for identification of GFP+ bone marrow-derived cells by direct fluorescence, protein immunohistochemistry and immunogold transmission electron microscopy. In both the intact and injured muscles, GFP positivity was determined in immune cells, mainly in macrophages, and in interstitial spindleshaped cells. Moreover, in the injured muscles, rare GFP+ endothelial cells of the blood vessels and newly formed myotubes and muscle fibres were present. Our results confirmed the ability of bone marrowderived cells to contribute to the cellular component of the satellite cell niche in the intact and regenerating skeletal muscle. These cells originated not only from haematopoietic stem cells, but obviously also from other stem or progenitor cells residing in the bone marrow, such as multipotent mesenchymal stromal cells and endothelial progenitors.

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Chiu, Chih-Hao, Tsan-Hsuan Chang, Shih-Sheng Chang, Gwo-Jyh Chang, Alvin Chao-Yu Chen, Chun-Ying Cheng, Su-Ching Chen, Jen-Fen Fu, Chih-Jen Wen, and Yi-Sheng Chan. "Application of Bone Marrow–Derived Mesenchymal Stem Cells for Muscle Healing After Contusion Injury in Mice." American Journal of Sports Medicine 48, no. 5 (March 5, 2020): 1226–35. http://dx.doi.org/10.1177/0363546520905853.

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Background: Skeletal muscle injuries are very common in sports medicine. Conventional therapies have limited clinical efficacy. New treatment methods should be developed to allow athletes to return to play with better function. Purpose: To evaluate the in vitro differentiation potential of bone marrow–derived mesenchymal stem cells and the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on muscle healing after contusion injury. Study Design: Controlled laboratory study. Methods: Bone marrow cells were flushed from both femurs of 5-week-old C57BL/6 mice to establish immortalized mesenchymal stem cell lines. A total of 36 mice aged 8 to 10 weeks were used to develop a muscle contusion model and were divided into 6 groups (6 mice/group) on the basis of the different dosages of IM2 cells to be injected (0, 1.25 × 105, and 2.5 × 105 cells with/without F-127 in 100 μL of phosphate-buffered saline). Histological analysis of muscle regeneration was performed, and the fast-twitch and tetanus strength of the muscle contractions was measured 28 days after muscle contusion injury, after injections of different doses of mesenchymal stem cells with or without the F-127 scaffold beginning 14 days after contusion injury. Results: The mesenchymal stem cell–treated muscles exhibited numerous regenerating myofibers. All the groups treated with mesenchymal stem cells (1.25 × 105 cells, 2.5 × 105 cells, 1.25 × 105 cells plus F-127, and 2.5 × 105 cells plus F-127) exhibited a significantly higher number of regenerating myofibers (mean ± SD: 111.6 ± 14.77, 133.4 ± 21.44, 221.89 ± 32.65, and 241.5 ± 25.95, respectively) as compared with the control group and the control with F-127 (69 ± 18.79 and 63.2 ± 18.98). The physiologic evaluation of fast-twitch and tetanus strength did not reveal differences between the age-matched uninjured group and the groups treated with various doses of mesenchymal stem cells 28 days after contusion. Significant differences were found between the control group and the groups treated with various doses of mesenchymal stem cells after muscle contusion. Conclusion: Mesenchymal stem cell therapy increased the number of regenerating myofibers and improved fast-twitch and tetanus muscle strength in a mouse model of muscle contusion. However, the rapid decay of transplanted mesenchymal stem cells suggests a paracrine effect of this action. Treatment with mesenchymal stem cells at various doses combined with the F-127 scaffold is a potential therapy for a muscle contusion. Clinical Relevance: Mesenchymal stem cell therapy has an effect on sports medicine because of its effects on myofiber regeneration and muscle strength after contusion injury.

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Vasyutin, Igor A., Aleksey V. Lyundup, and Sergey L. Kuznetsov. "Urine-Derived Stem Cells: Differentiation Potential into Smooth-Muscle Cells and Urothelial Cell." Annals of the Russian academy of medical sciences 74, no. 3 (July 8, 2019): 176–84. http://dx.doi.org/10.15690/vramn1131.

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Background: Tissue engineering of low urinary tract organs requires biopsy of urinary bladder material. The current study describes non-invasive approach of obtaining autologous stem cells from urine of healthy adults. These cells were studied for potential to differentiate into epithelial cells and smooth muscle cells of the urinary bladder. Aims: To describe properties of urine-derived stem cells (USCs) and investigate their differentiation potential for tissue engineering of low urinary tract organs. Materials and Methods: USCs were isolated from urine of healthy volunteers with centrifugation and seeded in media to 24-well plates. Expression of stem cells markers (CD73, CD90, CD105, CD34, CD45, CD29, CD44, CD54, SSEA4) by USCs was assessed with flow cytometry. Expression of specific markers of smooth muscle cells and urothelial cells was assessed with fluorescence microscopy with following computational image analysis. Results: Median number of USCs per 100 ml urine was 6. Doubling time for USC was 1.440.528 days (n=4) and there were 26.34.79 population doublings for USC cultures (n=4). Median expression of markers of postnatal stem cells was CD73 ― 79.8%, CD90 ― 56.6%, CD105 ― 40.7%, CD34 1.0%, CD45 2.0%, CD29 99.0%, CD44 99.0%, CD54 ― 97.7% and SSEA4 99.0%. Treatment of cells with high concentration of EGF in media with low concentration of FBS for 10 days increased cytokeratin (CK) expression to 24.9% for CK AE1/AE3 and to 7.6% for CK 7. Treatment of USCs with media inducing smooth muscle differentiation for 10 days increased expression of -smooth muscle actin to 79.6% and expression of calponin to 97.6%. Conclusions: USCs are cells that can be found in urine in small quantities. They have high proliferative potential and express markers of postnatal stem cells. Under effect of PDGF-BB and TGF- 1 they differentiate into smooth muscle cells.

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De Bari, Cosimo, Francesco Dell'Accio, Frank Vandenabeele, Joris R. Vermeesch, Jean-Marc Raymackers, and Frank P. Luyten. "Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane." Journal of Cell Biology 160, no. 6 (March 10, 2003): 909–18. http://dx.doi.org/10.1083/jcb.200212064.

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We have demonstrated previously that adult human synovial membrane-derived mesenchymal stem cells (hSM-MSCs) have myogenic potential in vitro (De Bari, C., F. Dell'Accio, P. Tylzanowski, and F.P. Luyten. 2001. Arthritis Rheum. 44:1928–1942). In the present study, we have characterized their myogenic differentiation in a nude mouse model of skeletal muscle regeneration and provide proof of principle of their potential use for muscle repair in the mdx mouse model of Duchenne muscular dystrophy. When implanted into regenerating nude mouse muscle, hSM-MSCs contributed to myofibers and to long term persisting functional satellite cells. No nuclear fusion hybrids were observed between donor human cells and host mouse muscle cells. Myogenic differentiation proceeded through a molecular cascade resembling embryonic muscle development. Differentiation was sensitive to environmental cues, since hSM-MSCs injected into the bloodstream engrafted in several tissues, but acquired the muscle phenotype only within skeletal muscle. When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor.

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Yang, Benjamin A., Jesus Castor-Macias, Paula Fraczek, Ashley Cornett, Lemuel A. Brown, Myungjin Kim, Susan V. Brooks, Isabelle M. A. Lombaert, Jun Hee Lee, and Carlos A. Aguilar. "Sestrins regulate muscle stem cell metabolic homeostasis." Stem Cell Reports 16, no. 9 (September 2021): 2078–88. http://dx.doi.org/10.1016/j.stemcr.2021.07.014.

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Larrick, James W., Jasmine W. Larrick, and Andrew R. Mendelsohn. "Reversal of Aged Muscle Stem Cell Dysfunction." Rejuvenation Research 19, no. 5 (October 2016): 423–29. http://dx.doi.org/10.1089/rej.2016.1875.

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Sambasivan, Ramkumar, and Shahragim Tajbakhsh. "Skeletal muscle stem cell birth and properties." Seminars in Cell & Developmental Biology 18, no. 6 (December 2007): 870–82. http://dx.doi.org/10.1016/j.semcdb.2007.09.013.

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Sousa-Victor, Pedro, Laura García-Prat, Antonio L. Serrano, Eusebio Perdiguero, and Pura Muñoz-Cánoves. "Muscle stem cell aging: regulation and rejuvenation." Trends in Endocrinology & Metabolism 26, no. 6 (June 2015): 287–96. http://dx.doi.org/10.1016/j.tem.2015.03.006.

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Fu, Xin, Huating Wang, and Ping Hu. "Stem cell activation in skeletal muscle regeneration." Cellular and Molecular Life Sciences 72, no. 9 (January 9, 2015): 1663–77. http://dx.doi.org/10.1007/s00018-014-1819-5.

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Meiliana, Anna, Nurrani Mustika Dewi, and Andi Wijaya. "Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging." Indonesian Biomedical Journal 7, no. 2 (August 1, 2015): 73. http://dx.doi.org/10.18585/inabj.v7i2.73.

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BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

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