Human Muscle Satellite Cells

Author by : Anne Baroffio
Languange : en
Publisher by : Unknown
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It S A Jungle Out There

Author by : Dane Lund
Languange : en
Publisher by : Unknown
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Description : Extracellular Matrix: Mammalian skeletal muscle is notable for both its highly ordered biophysical structure and its regenerative capacity following trauma. Critical to both of these features is the specialized muscle extracellular matrix (ECM), comprising both the multiple concentric sheaths of connective tissue surrounding structural units from single myofibers to whole muscles and the dense interstitial matrix that occupies the space between them. ECM-dependent interactions affect all activities of the resident muscle stem cell population, the satellite cell, from the maintenance of quiescence and stem cell potential to the regulation of proliferation and differentiation. This review will focus on the role of the extracellular matrix in muscle regeneration, with a particular emphasis on regulation of satellite cell activity. Cell Invasion: The twenty-five known matrix metalloproteases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteases (TIMPs), mediate cell invasion through the extracellular matrix (ECM). In a comparative 3D assay, we analyzed human and mouse satellite cells’ competence to invade an artificial ECM (collagen I). We identified a single MMP that: 1) is expressed by human muscle satellite cells; 2) is induced at the mRNA/protein level by adhesion to collagen I; and 3) is necessary for invasion into a collagen I matrix. Interestingly, murine satellite cells neither express this MMP, nor invade the collagen matrix. However, exogenous human MMP-14 is not sufficient to induce invasion of a collagen matrix by murine cells, emphasizing species differences.


Vertebrate Myogenesis

Author by : Beate Brand-Saberi
Languange : en
Publisher by : Springer
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Description : This book addresses the differentiation control of skeletal muscle in different locations of the vertebrate body Particular attention is paid to novel regulatory molecules and signals as well as the heterogeneity of origin that have revealed a developmental overlap between skeletal and cardiac muscle. Different functional muscle groups are the product of the evolution of the vertebrate classes, making a phylogenetic comparison worthwhile for understanding the role of muscle stem cells and precursors in myogenesis. New insights into the hierarchy of transcription factors, particularly in the context of these different muscle groups have been gained from detailed investigations of the spatio-temporal and regulatory relationships derived from mouse and zebrafish genetics and avian microsurgery. Importantly, epigenetic mechanisms that have surfaced recently, in particular the role of MyomiRs, are also surveyed. With an eye to the human patient, encouraging results have been generated that identify parallels between embryonic myogenesis and regenerating myofibers due to common regulatory molecules. On the other hand, both processes differ considerably in quality and complexity of the processes employed. Interestingly, the heterogeneity in embryonic sources from which skeletal muscle groups in the vertebrate including the human body take origin is paralleled by differences in their susceptibility to particular muscle dystrophies as well as by the characteristics of the satellite cells involved in regeneration. The progress that has been made in the field of muscle stem cell biology, with special focus on the satellite cells, is outlined in this book by experts in the field. The authors review recent insights of the heterogeneous nature of these satellite cells regarding their gene signatures and regeneration potential. Furthermore, an improved understanding of muscle stem cells seems only possible when we study the impact of the cell environment on efficient stem cell replacement therapies for muscular dystrophies, putting embryological findings from different vertebrate classes and stem cell approaches into context.


Regulation Of Skeletal Muscle Satellite Cell Proliferation By Nadph Oxidase

Author by : Mahroo Mofarrahi
Languange : en
Publisher by : Unknown
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Description : "Skeletal satellite cells are adult stem cells located among muscle fibers. Proliferation, migration and subsequent differentiation of these cells are critical steps in the repair of muscle injury. We document in this study the roles and mechanisms through which the NAPDH oxidase complex regulates skeletal satellite cell proliferation. The NADPH oxidase subunits Nox2, Nox4, p22phox, p47phox and p67 phox were detected in primary human and murine skeletal muscle satellite cells. In human satellite cells, NADPH oxidase-fusion proteins were localized in the cytosolic and membrane compartments of the cell, except for p47 phox, which was detected in the nucleus. In proliferating subconfluent satellite cells, both Nox2 and Nox4 contributed to O2- production. However, Nox4 expression was significantly attenuated in confluent cells and in differentiated myotubes. Proliferation of satellite cells was significantly reduced by antioxidants (N-acetylcysteine and apocynin), inhibition of p22phox expression using siRNA oligonucleotides, and reduction of Nox4 and p47phox activities with dominant-negative vectors resulted in attenuation of activities of the Erk1/2, PI-3 kinase/AKT and NFkappaB pathways and significant reduction in cyclin D1 levels. We conclude that NADPH oxidase is expressed in skeletal satellite cells and that its activity plays an important role in promoting proliferation of these cells." --


Lentivector Mediated Transfer Of Bmi 1 And Telomerase In Muscle Satellite Cells Yields A Duchenne Myoblast Cell Line With Long Term Genotypic And Phenotypic Stability

Author by : Christophe Cudré-Mauroux
Languange : en
Publisher by : Unknown
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Description : Conditionally immortalized human cells are valuable substrates for basic bilogic studies, as well as for the production of specific proteins and for the creation of bioartificial organs. We previously demonstrated that the lentivector-mediated transduction of immortalizing genes into human primary cells is an efficient method for obtaining such cell lines. Here, we used human muscle satellite cells as model targets to examine the impact of the transduced genes on the genotypic and phenotypic characteristics of the immortalized cells. The most commonly used immortalizing gene, the SV40 large T antigen (T-Ag), was extremely efficient at inducing the continuous growth of primary myoblasts, but the resulting cells rapidly accumulated major chromosomal aberrations and exhibited profound phenotypic changes. In contrast, the constitutive expression of telomerase and Bmi-1 in satellite cells from a control individual and from a patient suffering from Duchenne's muscular dystrophy yielded cell lines that remained diploid and conserved their growth factor dependence for proliferation. However, despite the absence of detectable cytogenetic abnormalities, clones derived from satellite cells of a control individual exhibited a differentiation block "in vitro". In contrast, a Duchenne-derived cell line exhibited all the phenotypic characteristics of its primary parent, including an ability to differentiate fully into myotubes when placed in proper culture conditions. This cell line should constitute a useful reagent for a wide range of studies aimed at this disease.


Lentivector Mediated Transfer Of Bmi 1 And Telomerase In Muscle Satellite Cells Yields A Duchenne Myoblast Cell Line With Long Term Genotypic And Phenotypic Stability

Author by : Anonim
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 31
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Description : Conditionally immortalized human cells are valuable substrates for basic bilogic studies, as well as for the production of specific proteins and for the creation of bioartificial organs. We previously demonstrated that the lentivector-mediated transduction of immortalizing genes into human primary cells is an efficient method for obtaining such cell lines. Here, we used human muscle satellite cells as model targets to examine the impact of the transduced genes on the genotypic and phenotypic characteristics of the immortalized cells. The most commonly used immortalizing gene, the SV40 large T antigen 8T-Ag), was extremely efficient at inducing the continuous growth of primary myoblasts, but the resulting cells rapidly accumulated major chromosomal aberraions and exhibited profound phenotypic changes. In contrast, the constitutive expression of telomerase and Bmi-1 in satellite cells from a control individual and from a patient suffering from Duchenne's muscular dystrophy yielded cell lines that remained dipliid and conserved their growth factor dependence for proliferation. However, despite the absence of detectable cytogenetic abnormalities, clones derived from satellite cells of a control individual exhibited a didderentiation block "in vitro". In contrast, a Duchenne-derived cele line exhibited all the phenotypic characteristics of its primary parent, including an ability to differentiate fully into myotubes when placed in proper culture conditions. This cell line should constitute a useful reagent for a wide range of studies aimed at this disease.


Studies Of Skeletal Muscle Satellite Cell Death And Renewal

Author by : Gregory William Charville
Languange : en
Publisher by : Unknown
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Total Read : 30
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Description : Skeletal muscle is an abundant tissue, accounting for 42% of the body mass of the average adult male human, and is required to generate the force necessary for movement and posture. The regeneration of skeletal muscle tissue in mammals is accomplished by a rare population of muscle-resident adult stem cells known as satellite cells. These satellite cells primarily reside in a dormant state and are prompted to carry-out their regenerative function by an injury to the neighboring muscle tissue. Atrophy and impaired regeneration of skeletal muscle are significant comorbidities of aging and chronic illness. This dissertation describes and interprets studies of skeletal muscle stem cell biology with particular attention paid to molecular mechanisms that influence stem cell-fate during regeneration in healthy and diseased contexts. The hypothesis that changes in stem cell regenerative potential underlie the poor tissue repair observed in aged animals is explored through comparisons of young and old cells. These studies identify a unique mitotic cell death phenomenon that occurs specifically within old cells as a consequence of age-associated changes in the satellite cell environment. In additional analyses, broad characterizations of gene expression in human satellite cells are leveraged to develop pharmacologic methods for controlling cell-fate to enhance the regenerative potential of purified cells. These analyses also provide insight into human-specific mechanisms of satellite cell-mediated myogenesis. The final series of studies uses satellite cells as a model system to examine cell-fate determination during stem cell divisions that give rise to daughter cells with divergent fates. These so-called asymmetric cell divisions are characterized specifically in terms of the unique patterns of chromosome segregation observed to coincide with regulation of muscle stem cell fate.


Atlas Of The Ultrastructure Of Diseased Human Muscle

Author by : W G P Mair
Languange : en
Publisher by : Elsevier
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Description : Atlas of the Ultrastructure of Diseased Human Muscle provides a general view of the ultrastructure of normal and diseased human muscle. This book contains five chapters that illustrate the changes that take place in common pathological conditions and outline the patterns of change, which occur in particular diseases. Chapter 1 describes the ultrastructure of normal striated muscle and the extra-ocular and cardiac muscle. This chapter also deals with skeletal and cardiac muscle of the human fetus. Chapter 2 examines the changes in the ultrastructure of muscle fibers, including changes in myofibrils, mitochondria, lipid bodies, plasma, and basement membranes. Chapters 3 and 4 evaluate the changes in blood capillaries, interstitial tissue of muscle, nerves, motor end plates, and muscle spindles. Chapter 5 discusses the ultrastructural changes in various muscle diseases, such as denervation atrophy of muscle, muscular dystrophies, polymyositis, and congenital myopathies.


Skeletal Muscle

Author by : Henning Schmalbruch
Languange : en
Publisher by : Springer Science & Business Media
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Description : This volume is intended to cover research in the field of muscle morphology since publication of the previous edition by Haggquist in 1956. The development of new techniques, coupled with an intensified interest in muscle, has resulted in a vast literature which no single person could review, especially within the limitations of one volume. When I accepted the flattering offer to write a new edition, I quickly abandoned any hope of a comprehensive review. Instead, I tried to consider, within my limits, those lines of research which I believe to be important for the understanding of mammalian and ultimately human muscles under normal, experimental, and pathological conditions. It would be naive to suggest that muscle can be adequately described in purely morphologi cal aspects; I would characterize the results of my effort as "muscle as seen with the eyes of a morphologist". It gives me pleasure to acknowledge the help of several colleagues who read and commented on drafts of individual chapters: Dr. Brenda Eisenberg, Chicago; Dr. Else Nygaard, Copenhagen; Dr. Stefano Schiaffino, Padova; Dr. Michael Sjostrom, Umea; Dr. Lars~Erik Thornell, Umea. None of these individ uals can be held responsible for any error or obscurity that persists. Indeed, without their assistance there would have been more. I also thank those col leagues who allowed me to include their published and unpublished material; their names, and also those of the publishers who kindly granted copyright permission, are given in the individual figure captions.


Using Synthetic Rna To Overexpress Pax7 In Human Induced Pluripotent Stem Cells To Produce Skeletal Muscle Progenitors

Author by : Shahab Younesi
Languange : en
Publisher by : Unknown
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Description : Skeletal muscle myofibers contain muscle stem cells called satellite cells that express the transcription factor PAX7, and regenerate muscle after acute injury. These skeletal muscle progenitor cells (SMPCs), or satellite cells in the adult muscle, lie outside the muscle fiber and refurbish the endogenous muscle stem cells upon damage. Human pluripotent stem cells (hPSCs) have enormous potential for use in regenerative medicine, especially for muscle wasting diseases like DMD. In DMD, the satellite cells become exhausted leading to failed regenerative ability. Once these muscle stem cells are depleted, damaged muscles are replaced by excessive fat and extracellular matrix deposition leading to muscle deterioration and fibrosis. One potential target to replenish exhausted muscle stem cells in patients with DMD is to generate an equivalent source from hPSCs. The myogenic activity from SMPCs derived from hPSCs is currently not well understood. We evaluated human fetal muscle in order to better understand the timing and specification of human SMPCs during human development and compare to hPSC-derived SMPCs for in vitro and in vivo myogenic activity. We have also shown that PAX7 is present in week 9 and 17 fetal skeletal muscle tissue, which may be indicative of when SMPC differentiation occurs. hPSC-derived SMPCs will be developed by the use of directed differentiation and synthetic mRNA. We have cloned PAX7 coding region into a VEE vector to enable synthetic RNA mediated overexpression (OE) of PAX7 into pre-differentiated hiPSCs in various plating conditions. PAX7 expression exceeded 700 fold in some conditions. Understanding the developmental and molecular underpinnings of human skeletal myogenesis will provide roads into generating SMPCs from hPSCs for use in regenerative medicine.


Muscle Cell And Tissue

Author by : Kunihiro Sakuma
Languange : en
Publisher by : BoD – Books on Demand
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Description : In order to complete tissue regeneration, various cells (neuronal, skeletal and smooth) interact coordinately with each other. This book, Muscle Cell and Tissue - Current Status of Research Field, deals with current progress and perspectives in a variety of topics on the skeletal and smooth muscle, stem cells, regeneration, disease or therapeutics. Novel applications for cell and tissue engineering including cell therapy, tissue models and disease pathology modeling are introduced. This book also deals with the differentiation/de-differentiation process of vascular smooth muscle cells in health and disease. Furthermore, natural products to reverse metabolic syndromes are descriptively reviewed. These chapters can be interesting for graduate students, teachers, physicians, executives and researchers in the field of molecular biology and regenerative medicine.


Primary Mesenchymal Cells

Author by : F. Koller
Languange : en
Publisher by : Springer Science & Business Media
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Description : The human body contains many specialized tissues that are capable of fulfilling an incredible variety of functions necessary for our survival. This volume in the Human Cell Culture Series focuses on mesenchymal tissues and cells. The in vitro study of mesenchymal cells is perhaps the oldest form of human cell culture, beginning with the culturing of fibroblasts. Fibroblasts have long been generically described in the literature, arising from many tissue types upon in vitro cell culture. However, recent studies, many enabled by new molecular biology techniques, have shown considerable diversity in fibroblast type and function, as described within this volume. Mesenchymal tissue types that are described within include bone, cartilage, tendons and ligaments, muscle, adipose tissue, and skin (dermis). The proper function of these tissues is predominantly dependent upon the proper proliferation, differentiation, and function of the mesenchymal cells which make up the tissue. Recent advancements in primary human mesenchymal cell culture have led to remarkable progress in the study of these tissues. Landmark experiments have now demonstrated a stem cell basis for many of these tissues, and, furthermore, significant plasticity and inter-conversion of stem cells between these tissues, resulting in a great deal of contemporary excitement and controversy. Newly-developed mesenchymal cell culture techniques have even lead to novel clinical practices for the treatment of disease.


Muscle Biopsy

Author by : Challa Sundaram
Languange : en
Publisher by : BoD – Books on Demand
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Description : Investigation of muscle diseases has changed dramatically with the understanding of genetic basis of a wide range of muscle diseases. Muscle biopsy has become a powerful tool not only to provide diagnosis but to make tissue available for genetic studies and to basic scientists for biomedical research. Accurate interpretation of muscle biopsy to detect cell dysfunction/ damage/death or absence / abnormality of a protein or genetic defect by the sophisticated technologies is important to guide treatment of various muscle diseases. In this book on muscle biopsy various chapters deal with the procedure and interpretation of muscle biopsy, its use in the culture of myotubes and membrane transport studies.Muscle biopsy is an important technique to investigate mitochondrial dysfunction and the mitochondrial DNA integrity in oxidation. Phosphorylation in various metabolic diseases like obesity, type 2 diabetes mellitus and peripheral vascular disease is explored in the other chapters with detailed descriptions on methodology. This book provides the advances in the basic techniques of muscle biopsy for a neuroscientist.


Skeletal Muscle Repair And Regeneration

Author by : Stefano Schiaffino
Languange : en
Publisher by : Springer Science & Business Media
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Description : Since the middle of the last century we have progressively built up a comprehensive descriptive model of the allied mechanisms that maintain our muscles at a size and strength appropriate to the functional demands upon them and that rapidly repair damaged muscles. This volume is an assemblage of the collective experience from the pick of major research groups investigating these aspects of muscle cell biology. It provides up-to-date coverage and presents a broad range of topics.


Age Related Behaviour Of Human Myoblasts In Vitro

Author by : Tomasz Evan George
Languange : en
Publisher by : Unknown
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Description : Ageing is characterised by a loss of muscle mass (sarcopenia). The mechanisms contributing to this loss are not known. One theory is that sarcopenia is facilitated by impaired regeneration after contraction-induced injury. Muscle repair is mediated by satellite cells (the muscle stem cells). Satellite cells, also termed myoblasts, from both young and old donor animals have been shown to proliferate in a similar manner in vitro and populate the regenerating muscles of young animals. This has lead to the suggestion that the satellite cells themselves are not affected by age. However, mouse satellite cell behaviour does seem to be impaired by factors in the aged circulation after extreme muscle damage. Whether behaviour of human satellite cells/myoblasts are influenced by the ageing process is not clear. This thesis has studied human myoblasts derived from muscle biopsy samples taken from elderly and young individuals. A cell culture approach was developed to study myoblasts in vitro. The system allowed for culture in human serum so that myoblasts could be exposed to a young or elderly circulatory milieu by adding serum obtained from elderly or young individuals to the culture conditions. -- No differences were observed in myoblast adherence, proliferation, differentiation or myotube size between cells derived from elderly and young biopsies, when freshly isolated from biopsy tissue. Myogenic progression was examined at early timepoints, using % desmin expression as a marker of muscle cells and % Ki67 expression to mark proliferation. The time course of muscle marker expression was very consistent between all biopsies examined with around 60% of cells staining positive for desmin after three days and 70-85% after seven days. The time course of Ki67 was more variable with values ranging from 15-50% at day three and 20-80% at day seven, this was the case in both young and elderly serum conditions.


Skeletal Muscle Structure Function And Plasticity

Author by : Richard L. Lieber
Languange : en
Publisher by : Lippincott Williams & Wilkins
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Description : In its Second Edition, this text addresses basic and applied physiological properties of skeletal muscle in the context of the physiological effects from clinical treatment. Many concepts are expanded and recent studies on human muscle have been added. This new edition also includes more clinically relevant cases and stories. A two-page full color insert of muscle sections is provided to ensure integral understanding of the concepts presented in the text. Anyone interested in human movement analysis and the understanding of generation and control from the musculoskeletal and neuromuscular systems in implementing movement will find this a valuable resource.


Craniofacial Muscles

Author by : Linda K. McLoon
Languange : en
Publisher by : Springer Science & Business Media
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Total Read : 33
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Description : Of the approximately 640 muscles in the human body, over 10% of them are found in the craniofacial region. The craniofacial muscles are involved in a number of crucial non-locomotor activities, and are critical to the most basic functions of life, including vision, taste, chewing and food manipulation, swallowing, respiration, speech, as well as regulating facial expression and controlling facial aperture patency. Despite their importance, the biology of these small skeletal muscles is relatively unexplored. Only recently have we begun to understand their unique embryonic development and the genes that control it and characteristic features that separate them from the skeletal muscle stereotype. This book is the most comprehensive reference to date on craniofacial muscle development, structure, function, and disease. It details the state-of-the-art basic science of the craniofacial muscles, and describes their unique response to major neuromuscular conditions. Most importantly, the text highlights how the craniofacial muscles are different from most skeletal muscles, and why they have been viewed as a distinct allotype. In addition, the text points to major gaps in our knowledge about these very important skeletal muscles and identified key gaps in our knowledge and areas primed for further study and discovery.


Cellular And Molecular Changes Following Skeletal Muscle Damage

Author by : Robert D. Hyldahl
Languange : en
Publisher by : Unknown
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Description : Skeletal muscle is dynamic and actively regenerates following damage or altered functional demand. Regeneration is essential for the maintenance of muscle mass and, when dysregulated as a result of disease or aging, can lead to losses in functional capacity and increased mortality. Limited data exist on the molecular mechanisms that govern skeletal muscle regeneration in humans. Therefore, the overall objective of this dissertation was to characterize early molecular alterations in human skeletal muscle to strenuous exercise known to induce a muscle regenerative response. Thirty-five subjects completed 100 eccentric (muscle lengthening) contractions (EC) of the knee extensors with one leg and muscle biopsies were taken from both legs 3 h post-EC. The sample from the non-EC leg served as the control. A well-powered transcriptomic screen and network analysis using Ingenuity Pathway software was first conducted on mRNA from the biopsy samples. Network analysis identified the transcription factor NF-kappaB (NF-kB) as a key molecular element affected by EC. Conformational qRT-PCR confirmed alterations in genes associated with NF-kappaB. A transcription factor ELISA, using nuclear extracts from EC and control muscle samples showed a 1.6 fold increase in NF-kB DNA binding activity following EC. Immunohistochemical experiments then localized the majority of NF-kB positive nuclei to cells in the interstitium, which stained positive for markers of pericyte cells and not satellite cells. To ascertain the mechanistic significance of NF-kB activation following muscle damage, in vitro analyses were carried out using a novel primary pericyte/myoblast co-culture model. Primary pericyte/myoblast co-culture experiments demonstrated that pericytes, transfected with a DNA vector designed to drive NF-kB activation, enhanced proliferation and inhibited myogenic differentiation of co-cultured skeletal muscle myoblasts. Furthermore, reduced NF-kB activation led to enhanced myogenic potential of primary pericytes. Taken together, the data in this dissertation suggest that NF-kB dependent signaling in pericytes regulates myogenic differentiation in a cell- and non-cell autonomous manner and may affect the early regenerative response following muscle damage by inhibiting differentition and promoting proliferation of muscle satellite cells.


Effects Of The Local Organ And Systemic Environments On Stem Cell Aging

Author by : Morgan Erik Carlson
Languange : en
Publisher by : Unknown
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Description : This work uncovers mechanisms of aging within stem cell niches that are evolutionarily conserved between mice and humans, and affect both embryonic and adult stem cells. Specifically, the effects of aged muscle and systemic niches on key molecular identifiers of regenerative potential of human embryonic stem cells (hESCs) and postnatal muscle stem cells (satellite cells) were examined. Results reveal that aged differentiated niches dominantly inhibit the expression of Oct4 in hESC and Myf-5 in activated satellite cells, and reduce proliferation and myogenic differentiation of both embryonic and tissue specific adult stem cells (ASCs). Therefore, the ability of hESCs, and the more differentiated myogenic ASCs to contribute to tissue repair in the old will be restricted, due to the conserved inhibitory influence of aged differentiated niches. Additionally, this work establishes that hESC-derived factors enhance the regenerative potential of both young and importantly, aged muscle stem cells in vitro and in vivo; thus, suggesting that the regenerative outcome of stem cell-based replacement therapies will be determined by a balance between negative influences of aged tissues on transplanted cells and positive effects of embryonic cells on the endogenous regenerative capacity.


Role Of Stem Cells In Skeletal Muscle Development Regeneration Repair Aging And Disease

Author by : Pura Muñoz-Cánoves
Languange : en
Publisher by : Frontiers Media SA
Format Available : PDF, ePub, Mobi
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Description : Adult stem cells are responsible for tissue regeneration and repair throughout life. Their quiescence or activation are tightly regulated by common signalling pathways that often recapitulate those happening during embryonic development, and thus it is important to understand their regulation not only in postnatal life, but also during foetal development. In this regard, skeletal muscle is an interesting tissue since it accounts for a large percentage of body mass (about 40%), it is highly amenable to intervention through exercise and it is also key in metabolic and physiological changes underlying frailty susceptibility in the elderly. While muscle-resident satellite cells are responsible for all myogenic activity in physiological conditions and become senescent in old age, other progenitor cells such as mesoangioblasts do seem to contribute to muscle regeneration and repair after tissue damage. Similarly, fibro-adipogenic precursor cells seem to be key in the aberrant response that fills up the space left from atrophied muscle mass and which ends up with a dysfunctional muscle having vast areas of fatty infiltration and fibrosis. The complex interplay between these stem/progenitor cell types and their niches in normal and pathological conditions throughout life are the subjects of intense investigation. This eBook highlights recent developments on the role of stem cells in skeletal muscle function, both in prenatal and postnatal life, and their regulation by transcriptional, post-transcriptional and epigenetic mechanisms. Additionally, it includes articles on interventions associated with exercise, pathological changes in neuromuscular diseases, and stem cell aging.


Repair And Adaptation Of Aged Skeletal Muscle To Nonpathological Muscle Damage

Author by : Jacob R. Sorensen
Languange : en
Publisher by : Unknown
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Total Read : 10
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Description : The age-related loss of skeletal muscle mass and function is accompanied by a decline in regenerative capacity. The processes that facilitate healthy muscle repair are complex, involving several phases of degradation and rebuilding of muscle tissue and the surrounding microenvironment. Specifically, myogenic progenitor cells known as satellite cells are the most influential in repairing damaged muscle tissue. Following injury, satellite cells become activated and migrate, proliferate and fuse with mature skeletal muscle fibers to restore homeostasis to the tissue. However, satellite cells do not act in isolation, a robust inflammatory response is necessary to facilitate successful and rapid healing. Macrophages are one of the first and most abundant immune cells to infiltrate damaged skeletal muscle tissue. Primarily, macrophages adapt to a proinflammatory state to clear the area of cellular debris, promote degradation of the extracellular matrix and stimulate satellite cell activation and proliferation. Afterwards, a timely transition to an anti-inflammatory state directs rebuilding of the extracellular matrix and terminal differentiation of satellite cells. Indeed, the inhibition of macrophage activity leads to impaired healing and loss of skeletal muscle function. Little is known regarding the behavior of macrophages in aged skeletal muscle following injury in humans. Thus, the objective of this dissertation is to investigate the age-related response of macrophages in human skeletal muscle, and their role in the muscle repair.


Frontiers In Skeletal Muscle Wasting Regeneration And Stem Cells

Author by : Carlos Hermano J. Pinheiro
Languange : en
Publisher by : Frontiers Media SA
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Description : The search for knowledge on cellular and molecular mechanisms involved in skeletal muscle mass homeostasis and regeneration is an exciting scientific area and extremely important to develop therapeutic strategies for neuromuscular disorders and conditions related to muscle wasting. The mechanisms involved in the regulation of skeletal muscle mass and regeneration consist of molecular signaling pathways modulating protein synthesis and degradation, bioenergetics alterations and preserved function of muscle stem cells. In the last years, different kinds of stem cells has been reported to be localized into skeletal muscle (satellite cells, mesoangioblasts, progenitor interstitial cells and others) or migrate from non-muscle sites, such as bone marrow, to muscle tissue in response to injury. In addition, myogenic progenitor cells are also activated in skeletal muscle wasting disorders. The goal of this research topic is to highlight the available knowledge regarding skeletal muscle and stem cell biology in the context of both physiological and pathological conditions. Our purpose herein is to facilitate better dissemination of research into skeletal muscle physiology field. Frontiers in Physiology is a journal indexed in: PubMed Central, Scopus, Google Scholar, DOAJ, CrossRef.


A Neuron Specific Protein Found In Skeletal Muscle

Author by : Raffaele Pilla
Languange : en
Publisher by : Universal-Publishers
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Description : Growth Associated Protein 43 (GAP-43), isolated from rat brain and considered a neuronal marker, is involved in neurite branching, cytoskeleton remodelling, neuronal development and protection. However, GAP-43 mRNA was found in embryonic chicken cells positive to meromyosin, as well as in human satellite cells, myoblasts and myotubes deriving from healthy or dystrophic muscles. Despite these findings, there is no clear evidence about its localization or relationship with other muscle proteins. The aim of this study was to investigate GAP-43 protein expression and localization in C2C12 cells and mice skeletal muscle fibers, using immunoblot and immunofluorescence protocols for confocal mycroscopy. Immunoblot analyses show the presence of GAP-43 in C2C12 cell homogenates as well as in mature muscle fibers. Immunofluorescent images reveal that the protein is localized nearby the external nuclear membranes in C2C12 myoblasts, while in C2C12 myotubes, it has been detected on muscular streaks, in a regular double strand pattern. This localization has been found also in Extensor Digitorum Longus fibers isolated from 1 week, 1 and 24 months old mice. In isolated adult mouse fibers, GAP-43 localization appears to be in relationship with crucial proteins such as triadin, alfa-actinin, RyR, DHPR, as well as mitochondria. In addition, cross-specimen analyses on skeletal muscle cells and mature fibers from Xenopus Laevis (amphibian), rat and human were performed, in order to interpret the results from an evolutionary point of view. In conclusion, these preliminary data confirm the presence of GAP-43 in all the analyzed skeletal muscles, and its localization supports the hypothesis of a possible new functional role in the muscle excitation-contraction coupling process.


Journal Of Cell Science

Author by : Anonim
Languange : en
Publisher by : Unknown
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Description :


Embryonic And Adult Stem Cells Explored Through Microfluidics And Biological Manipulation

Author by : Eric Benjamin Pierre Jabart
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 23
Total Download : 102
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Description : Part I - A Microfluidic Method for the Selection of Undifferentiated Human Embryonic Stem Cells and in Situ Analysis Conventional cell-sorting methods such as FACS or MACS can suffer from certain shortcomings such as lengthy sample preparation time, cell modification through antibody labeling, and exposure to high shear forces or metallic microparticles. In light of these drawbacks, we have recently developed a novel, label-free, microfluidic platform that can not only sort cells with minimal sample preparation but also enable analysis of cells in situ. In contrast to MACS or FACS, cells sorted by our method have very high viability (~90%). In this part of my thesis, I first describe existing antibody-functionalized microfluidic devices for cell sorting as well those designed for human embryonic stem cell (hESC) sorting. I then demonstrate the utility of our platform to sort undifferentiated human embryonic stem cells (hESCs) from a heterogeneous population, achieving ~60% average purity of the cells expressing a marker of interest. I also discuss future strategies to improve sorting efficiency. Overall, our platform technology could be applied to other cell types beyond hESCs and to a variety of heterogeneous cell populations. Part II - Attenuation of TGF-[beta] Signaling via Incorporation of a Dominant-negative TGF-[beta] Type II Receptor Promotes Improved Muscle Regeneration in Murine Skeletal Myoblasts Skeletal muscle stem cells known as satellite cells are responsible for muscle regeneration. Upon muscle injury or exercise, quiescent satellite cells become activated, proliferate as myogenic precursors, differentiate into myoblasts, and ultimately fuse into new, multinucleated myofibers. Unfortunately, this paradigm breaks down with aging and multiple factors contribute to a build-up of scar tissue instead of new muscle. Among these negative contributors are some members of the TGF-[beta] family of signaling molecules. After an introduction to muscle regeneration and satellite cells, the adult skeletal muscle stem cells, I will discuss how biomaterials can help improve muscle regeneration and recent advances in combating TGF-[beta]-induced impairment in muscle repair. I will then discuss the work I have done in improving skeletal muscle repair by attenuating the effects of TGF-[beta] signaling via incorporation of a dominant-negative TGF-[beta] type II receptor.