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Satellite Cells (satellite + cell)

Distribution by Scientific Domains

Life Sciences	66%
Medical Sciences	33%

Kinds of Satellite Cells

muscle satellite cell

Selected Abstracts

The Expression Profile of Myogenic Transcription Factors in Satellite Cells from Denervated Rat Muscle

BRAIN PATHOLOGY, Issue 2 2002
Annette Maier;
The muscle-specific transcription factors of the MyoD family are altered after denervation. In order to determine whether this shift takes place in satellite cells (SC), we investigated the expression pattern of MyoD, myf5, myogenin, and MRF4 in SC. Hindlimb muscles of rats were denervated for 2 days to 4 weeks. SC were isolated, pooled and the transcription of all 4 factors was assessed by RT-PCR. Protein expression was assessed in histological sections of soleus and anterior tibial (TA) muscles; SC were identified by M-cadherin. Pooled SC from innervated muscles expressed myf5 mRNA, and very weakly MyoD and myogenin mRNA. MyoD and myogenin protein was found in only few SC. After denervation, pooled SC expressed myf5 mRNA, and very weakly myogenin and MRF4 mRNA. Myogenin protein was found in less than about 10% of the cells, whereas MRF4 protein was absent from SC. We conclude that the presence of myf5 and the absence of MyoD and MRF4 protein in SC after denervation indicated the quiescent state of the cell cycle. A subset of SC has additionally acquired myogenin. SC after denervation might be less easily recruited into the mitotic cycle than SC from normal muscle, rendering regeneration of denervated muscle less efficient than normal muscle. [source]

In vitro measurement of post-natal changes in proliferating satellite cell frequency during rat muscle growth

ANIMAL SCIENCE JOURNAL, Issue 2 2010
Takahiro SUZUKI
ABSTRACT Satellite cells, resident myogenic stem cells found in postnatal skeletal muscle, are most abundant during early postnatal development and sharply decline in frequency thereafter to adult levels in mice and rats. Therefore, postnatal changes in satellite cell mitotic activities are important aspects for further understanding a muscle growth strategy. In large meat-production animals, however, the traditional in vivo proliferation assay may be less realistic because it requires intra-peritoneal (ip) injection of huge dosage of mutagenic nucleosides, 3H-labeled thymidine or bromodeoxyuridine (BrdU), at each age-time of sacrifice. We report in the present pilot study using rats that in vivo proliferation activity of satellite cells can be evaluated by an in vitro BrdU-incorporation assay in early cultures. Briefly, satellite cells were prepared from upper hind-limb and back muscles and maintained for 24 h with imposing by BrdU addition for the last 2 h, followed by the regular immunocytochemistry for determining BrdU-incorporated cell percentage. This in vitro assay demonstrated a rapid decrease in proliferating satellite cell frequency to the adult level during about 3-month period after birth, and yielded a high correlation to the measurements by the in vivo BrdU ip-injection method during the postnatal period examined from day-2 to month-11. The in vitro proliferation assay may be further adaptable for large domestic animals by the combination with a muscle biopsy technique that enables age-interval sampling from the same growing animals. [source]

Oestrogen receptor-alpha activation augments post-exercise myoblast proliferation

ACTA PHYSIOLOGICA, Issue 1 2010
A. Thomas
Abstract Aim:, Our laboratory has shown that oestrogen acts to augment myoblast (satellite cell) activation, proliferation and total number and that this may occur through an oestrogen receptor (OR)-mediated mechanism. The purpose of this study was to further investigate the mechanism of oestrogen influence on augmentation of post-exercise myoblast numbers through use of a specific OR-, agonist, propyl pyrazole triol (PPT). Methods:, Ovariectomized rats were used (n = 64) and separated into four groups: sham, oestrogen supplemented, agonist supplemented, and a combined oestrogen and agonist supplemented group. These groups were further subdivided into control (unexercised) and exercise groups. Surgical removal of white vastus and soleus muscles was performed 72 h post-exercise. Muscle samples were immunostained for the myoblast markers Pax7 and MyoD. Results:, A significant increase in total (Pax7-positive) and activated (MyoD-positive) myoblasts was found in all groups post-exercise. A further significant augmentation of total and activated myoblasts occurred in oestrogen supplemented, agonist supplemented and the combined oestrogen and agonist supplemented groups post-exercise in white vastus and soleus muscles relative to unsupplemented animals. Conclusion:, These results demonstrate that both oestrogen and the specific OR-, receptor agonist, PPT, can significantly and to similar degrees augment myoblast number and activation following exercise-induced muscle damage. This suggests that oestrogen acts through an OR-mediated mechanism to stimulate myoblast proliferation following exercise, with OR-, playing a primary role. [source]

Alterations of M-cadherin, neural cell adhesion molecule and , -catenin expression in satellite cells during overload-induced skeletal muscle hypertrophy

ACTA PHYSIOLOGICA, Issue 3 2006
M. Ishido
Abstract Aim:, Neural cell adhesion molecule (NCAM) and M-cadherin are cell adhesion molecules expressed on the surface of skeletal muscle satellite cell (SC). During myogenic morphogenesis, M-cadherin participates in mediating terminal differentiation and fusion of myoblasts by forming a complex with , -catenin and that NCAM contributes to myotube formation by fusion of myoblasts. Hypertrophy and hyperplasia of functionally overloaded skeletal muscle results from the fusion with SCs into the existing myofibres or new myofibre formation by SC,SC fusion. However, the alterations of NCAM, M-cadherin and , -catenin expressions in SCs in response to functional overload have not been investigated. Methods:, Using immunohistochemical approaches, we examined the temporal and spatial expression patterns of these factors expressed in SCs during the functional overload of skeletal muscles. Results:, Myofibres with SCs showing NCAM+/M-cadherin,, NCAM+/M-cadherin+ or NCAM,/M-cadherin+ were detected in overloaded muscles. The percentage changes of myofibres with SCs showing NCAM+/M-cadherin,, NCAM+/M-cadherin+ or NCAM,/M-cadherin+ were elevated in day-3 post-overloaded muscles, and then only the percentage changes of myofibres with SCs showing NCAM,/M-cadherin+ were significantly increased in day-7 post-overload muscles (P < 0.05). Both , -catenin and M-cadherin were co-localized throughout quiescent, proliferation and differentiation stages of SCs. Conclusion:, These results suggested that the expressions of NCAM, M-cadherin and , -catenin in SCs may be controlled by distinct regulatory mechanisms during functional overload, and that interactions among NCAM, M-cadherin and , -catenin in SCs may play important roles to contribute to overload-induced muscle hypertrophy via fusion with each other or into the existing myofibres of SCs. [source]

The expression patterns of Pax7 in satellite cells during overload-induced rat adult skeletal muscle hypertrophy

ACTA PHYSIOLOGICA, Issue 4 2009
M. Ishido
Abstract Aim:, Activated satellite cells (SCs) have the ability to reacquire a quiescent, undifferentiated state. Pax7 plays a crucial role in allowing activated SCs to undergo self-renewal. Because the increase in the SC population is induced during overload-induced skeletal muscle hypertrophy, it is possible that Pax7-regulated SC self-renewal is involved in the modulation of the SC population during the functional overload of skeletal muscles. However, the characteristics of the expression patterns of Pax7 in SCs during the functional overload of adult skeletal muscles are poorly understood. Methods:, Using immunohistochemical approaches, we examined the temporal and spatial expression patterns of Pax7 expressed in SCs during the functional overloading of rat skeletal muscles. Results:, The time course of Pax7 expression in SCs was similar to that of the expression of the differentiation regulatory factor myogenin during the early stage of functional overload. However, the percentage of SCs that expressed Pax7 was markedly higher than that of the SCs that expressed myogenin. Coexpression of Pax7 and myogenin was not detected in SCs. In addition, the expression of cyclin-dependent kinase inhibitor p21, which regulates cell cycle arrest and differentiation, was not detected in Pax7-positive SCs. Conclusion:, These results suggest that Pax7-regulated self-renewal of SCs may be induced during the early stage of functional overload and may contribute to modulating the SC population in hypertrophied muscles. Furthermore, it was suggested that the numbers of SCs which underwent self-renewal may be higher than that of SCs which were provided as the additional myonuclei for hypertrophying myofibres. [source]

Alterations of M-cadherin, neural cell adhesion molecule and , -catenin expression in satellite cells during overload-induced skeletal muscle hypertrophy

Effects of eccentric treadmill running on mouse soleus: degeneration/regeneration studied with Myf-5 and MyoD probes

ACTA PHYSIOLOGICA, Issue 1 2003
A.-S. Armand
Abstract Aim:, The aim of this report is to show that eccentric exercise under well-controlled conditions is an alternative model, to chemical and mechanical analyses, and analyse the process of degeneration/regeneration in mouse soleus. Methods:, For this, mice were submitted to a single bout of eccentric exercise on a treadmill down a 14° decline for 150 min and the soleus muscle was analysed at different times following exercise by histology and in situ hybridization in comparison with cardiotoxin-injured muscles. Results:, We analyse the regenerative process by detection of the accumulation of transcripts coding for the two myogenic regulatory factors, Myf-5 and MyoD, which are good markers of the activated satellite cells. From 24 h post-exercise (P-E), clusters of mononucleated Myf-5/MyoD-positive cells were detected. Their number increased up to 96 h P-E when young MyoD-positive myotubes with central nuclei began to appear. From 96 to 168 h P-E the number of myotubes increased, about 10-fold, the new myotubes representing 58% of the muscle cells (168 h P-E). Conclusion:, These results show that this protocol of eccentric exercise is able to induce a drastic degeneration/regeneration process in the soleus muscle. This offers the opportunity to perform biochemical and molecular analyses of a process of regeneration without muscle environment defects. The advantages of this model are discussed in the context of fundamental and therapeutical perspectives. [source]

Analysis of human muscle stem cells reveals a differentiation-resistant progenitor cell population expressing Pax7 capable of self-renewal

DEVELOPMENTAL DYNAMICS, Issue 1 2009
Bradley Pawlikowski
Abstract Studies using mouse models have established a critical role for resident satellite stem cells in skeletal muscle development and regeneration, but little is known about this paradigm in human muscle. Here, using human muscle stem cells, we address their lineage progression, differentiation, migration, and self-renewal. Isolated human satellite cells expressed ,7-integrin and other definitive muscle markers, were highly motile on laminin substrates and could undergo efficient myotube differentiation and myofibrillogenesis. However, only a subpopulation of the myoblasts expressed Pax7 and displayed a variable lineage progression as measured by desmin and MyoD expression. Analysis identified a differentiation-resistant progenitor cell population that was Pax7+/desmin, and capable of self-renewal. This study extends our understanding of the role of Pax7 in regulating human satellite stem cell differentiation and self-renewal. Developmental Dynamics 238:138,149, 2009. © 2008 Wiley-Liss, Inc. [source]

Muscle stem cells and model systems for their investigation

DEVELOPMENTAL DYNAMICS, Issue 12 2007
Nicolas Figeac
Abstract Stem cells are characterized by their clonal ability both to generate differentiated progeny and to undergo self-renewal. Studies of adult mammalian organs have revealed stem cells in practically every tissue. In the adult skeletal muscle, satellite cells are the primary muscle stem cells, responsible for postnatal muscle growth, hypertrophy, and regeneration. In the past decade, several molecular markers have been found that identify satellite cells in quiescent and activated states. However, despite their prime importance, surprisingly little is known about the biology of satellite cells, as their analysis was for a long time hampered by a lack of genetically amenable experimental models where their properties can be dissected. Here, we review how the embryonic origin of satellite cells was discovered using chick and mouse model systems and discuss how cells from other sources can contribute to muscle regeneration. We present evidence for evolutionarily conserved properties of muscle stem cells and their identification in lower vertebrates and in the fruit fly. In Drosophila, muscle stem cells called adult muscle precursors (AMP) can be identified in embryos and in larvae by persistent expression of a myogenic basic helix,loop,helix factor Twist. AMP cells play a crucial role in the Drosophila life cycle, allowing de novo formation and regeneration of adult musculature during metamorphosis. Based on the premise that AMPs represent satellite-like cells of the fruit fly, important insight into the biology of vertebrate muscle stem cells can be gained from genetic analysis in Drosophila. Developmental Dynamics 236:3332,3342, 2007. © 2007 Wiley-Liss, Inc. [source]

Signal modelization for improved precision of assessment of minimum and mean telomere lengths

ELECTROPHORESIS, Issue 2 2008
Elodie Ponsot Dr.
Abstract Telomere length is an important measure of cell and tissue regenerative capacities. The mean telomere length is classically used as global indicator of a tissue telomere length. In skeletal muscle, which is made of postmitotic myonuclei and satellite cells (muscle stem cells), minimum telomere length is also used to assess the telomere length of satellite cells and newly incorporated myonuclei. At present, the estimation of the method reproducibility during the assessment of mean and minimum telomere length using Southern blot analysis has never been documented. The aim of this report is to describe a signal modelization for improved precision of assessment of minimum and mean telomere lengths and to document the method reproducibility. Telomeres are assessed using a Southern technique where the gel is directly hybridized with the specific probe without the membrane-transferring step in order to prevent telomeric low signal loss. We found that the improved signal analysis for determination of telomere length is associated with coefficients of variation ranging from 1.37 to 4.29% for the mean telomeric restriction fragment (TRF) length and from 2.04 to 4.95% for the minimum TRF length. Improved method reproducibility would allow saving time and biological material as duplicate and triplicate measurement of the same sample is no longer required. [source]

Plasticity of human skeletal muscle: gene expression to in vivo function

EXPERIMENTAL PHYSIOLOGY, Issue 5 2007
Stephen D. R. Harridge
Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (Vmax), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing Vmax and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level. [source]

Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells

GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 7 2010
Christoph Lepper
Descendants of E9.5 Pax7-expressing (in red, ,-gal+) central dermomyotome cells contribute to myofibers (in green, MF-20+, a myosin heavy chain protein) in the E16.5 mouse embryo. Nuclei are blue (DAPI). The ,-gal+/MF-20_ cells that are intermingled with myofibers are likely myogenic progenitors. See the article by Lepper and Fan in this issue. [source]

Highlighted article: "Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells" by lepper and fan

GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 7 2010
Article first published online: 13 JUL 2010
No abstract is available for this article. [source]

Dermatan sulfate exerts an enhanced growth factor response on skeletal muscle satellite cell proliferation and migration

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004
Joan Villena
Skeletal muscle regeneration is a complex process in which many agents are involved. When skeletal muscle suffers an injury, quiescent resident myoblasts called satellite cells are activated to proliferate, migrate, and finally differentiate. This whole process occurs in the presence of growth factors, the extracellular matrix (ECM), and infiltrating macrophages. We have shown previously that different proteoglycans, either present at the plasma membrane or the ECM, are involved in the differentiation process by regulating growth factor activity. In this article, we evaluated the role of glycosaminoglycans (GAGs) in myoblast proliferation and migration, using C2C12, a satellite cell-derived cell line. A synergic stimulatory effect on myoblast proliferation was observed with hepatocyte growth factor (HGF) and fibroblast growth factor type 2 (FGF-2), which was dependent on cell sulfation. The GAG dermatan sulfate (DS) enhanced HGF/FGF-2-dependent proliferation at 1,10 ng/ml. However, decorin, a proteoglycan containing DS, was unable to reproduce this enhanced proliferative effect. On the other hand, HGF strongly increased myoblast migration. The HGF-dependent migratory process required the presence of sulfated proteoglycans/GAGs present on the myoblast surface, as inhibition of both cell sulfation, and heparitinase (Hase) and chondroitinase ABC (Chabc) treatment of myoblasts, resulted in a very strong inhibition of cell migration. Among the GAGs analyzed, DS most increased HGF-dependent myoblast migration. Taken together, these findings showed that DS is an enhancer of growth factor-dependent proliferation and migration, two critical processes involved in skeletal muscle formation. J. Cell. Physiol. 198: 169,178, 2004© 2003 Wiley-Liss, Inc. [source]

Relative roles of TGF-,1 and Wnt in the systemic regulation and aging of satellite cell responses

AGING CELL, Issue 6 2009
Morgan E. Carlson
Summary Muscle stem (satellite) cells are relatively resistant to cell-autonomous aging. Instead, their endogenous signaling profile and regenerative capacity is strongly influenced by the aged P-Smad3, differentiated niche, and by the aged circulation. With respect to muscle fibers, we previously established that a shift from active Notch to excessive transforming growth factor-beta (TGF-,) induces CDK inhibitors in satellite cells, thereby interfering with productive myogenic responses. In contrast, the systemic inhibitor of muscle repair, elevated in old sera, was suggested to be Wnt. Here, we examined the age-dependent myogenic activity of sera TGF-,1, and its potential cross-talk with systemic Wnt. We found that sera TGF-,1 becomes elevated within aged humans and mice, while systemic Wnt remained undetectable in these species. Wnt also failed to inhibit satellite cell myogenicity, while TGF-,1 suppressed regenerative potential in a biphasic fashion. Intriguingly, young levels of TGF-,1 were inhibitory and young sera suppressed myogenesis if TGF-,1 was activated. Our data suggest that platelet-derived sera TGF-,1 levels, or endocrine TGF-,1 levels, do not explain the age-dependent inhibition of muscle regeneration by this cytokine. In vivo, TGF-, neutralizing antibody, or a soluble decoy, failed to reduce systemic TGF-,1 and rescue myogenesis in old mice. However, muscle regeneration was improved by the systemic delivery of a TGF-, receptor kinase inhibitor, which attenuated TGF-, signaling in skeletal muscle. Summarily, these findings argue against the endocrine path of a TGF-,1-dependent block on muscle regeneration, identify physiological modalities of age-imposed changes in TGF-,1, and introduce new therapeutic strategies for the broad restoration of aged organ repair. [source]

Regenerative potential of human skeletal muscle during aging

AGING CELL, Issue 2 2002
Valérie Renault
Summary In this study, we have investigated the consequences of aging on the regenerative capacity of human skeletal muscle by evaluating two parameters: (i) variation in telomere length which was used to evaluate the in vivo turn-over and (ii) the proportion of satellite cells calculated as compared to the total number of nuclei in a muscle fibre. Two skeletal muscles which have different types of innervation were analysed: the biceps brachii, a limb muscle, and the masseter, a masticatory muscle. The biopsies were obtained from two groups: young adults (23 ± 1.15 years old) and aged adults (74 ± 4.25 years old). Our results showed that during adult life, minimum telomere lengths and mean telomere lengths remained stable in the two muscles. The mean number of myonuclei per fibre was lower in the biceps brachii than in the masseter but no significant change was observed in either muscle with increasing age. However, the number of satellite cells, expressed as a proportion of myonuclei, decreased with age in both muscles. Therefore, normal aging of skeletal muscle in vivo is reflected by the number of satellite cells available for regeneration, but not by the mean number of myonuclei per fibre or by telomere lengths. We conclude that a decrease in regenerative capacity with age may be partially explained by a reduced availability of satellite cells. [source]

Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion-affected expression, and impaired regenerative axonal growth

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009
Bettina A. Buhren
Abstract Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice. © 2009 Wiley-Liss, Inc. [source]

Current opportunities and challenges in skeletal muscle tissue engineering

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2009
Merel Koning
Abstract The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high proneness to muscular differentiation, in particular exhibiting the same characteristics and function as its donor muscle. This suggests that it is important to use an appropriate progenitor cell, especially in TE facial muscles, which have a exceptional anatomical and fibre composition compared to other skeletal muscle. Muscle TE requires an instructive scaffold for structural support and to regulate the proliferation and differentiation of muscle progenitor cells. Current literature suggests that optimal scaffolding could comprise of a fibrin gel and cultured monolayers of muscle satellite cells obtained through the cell sheet technique. Tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen, carbon dioxide, nutrients and waste products. Finally, functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural cells. To reach this, it seems important to apply optimal electrical, chemotropic and mechanical stimulation during engineering and discover other factors that influence its formation. Thus, in addition to approaches for myogenesis, we discuss the current status of strategies for angiogenesis and neurogenesis of TE muscle constructs and the significance for future clinical use. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Long-term morphometric and immunohistochemical findings in human free microvascular muscle flaps,

MICROSURGERY, Issue 1 2004
M. Susanna C. Kauhanen M.D., Ph.D.
Reinnervation, muscle regeneration, density of microvessels, and muscle-type specific atrophy were studied 3,4 years after surgery in surgically nonreinnervated free microvascular muscle flaps to 13 patients transplanted to the upper or lower extremities. Routine histology and immunohistochemistry for PGP 9.5 and S-100 (neuronal markers), Ki-67 (cell proliferation), myosin (muscle fiber types), and CD-31 (endothelium) were carried out, and results were analyzed morphometrically. Three to 4 years after surgery, severe atrophy of predominantly slow-type fibers was seen in 9 cases. In 4 cases, muscle-fiber diameter and fiber-type distribution were close to normal. Long intraoperative muscle ischemia and postoperative immobilization were associated with poor muscle bulk in flaps. The density of microvessels in flaps did not differ from control muscles. PGP 9.5 and S-100 immunopositive nerve fibers were detected in 7 patients. Reinnervation was associated with good muscle bulk. In 4 patients, activation of satellite cells was evident. The results suggest that in some cases, spontaneous reinnervation may occur in free muscle flaps, and that several years after microvascular free flap transfer, the muscle still attempts to regenerate. © 2004 Wiley-Liss, Inc. [source]

Signaling satellite-cell activation in skeletal muscle: Markers, models, stretch, and potential alternate pathways

MUSCLE AND NERVE, Issue 3 2005
Ashley C. Wozniak BSc
Abstract Activation of skeletal muscle satellite cells, defined as entry to the cell cycle from a quiescent state, is essential for normal growth and for regeneration of tissue damaged by injury or disease. This review focuses on early events of activation by signaling through nitric oxide and hepatocyte growth factor, and by mechanical stimuli. The impact of various model systems used to study activation and the regulation of satellite-cell quiescence are placed in the context of activation events in other tissues, concluding with a speculative model of alternate pathways signaling satellite-cell activation. Muscle Nerve, 2005 [source]

The expression pattern of PKC, in satellite cells of normal and regenerating muscle in the rat

NEUROPATHOLOGY, Issue 3 2009
Seiji Tokugawa
Protein kinase C (PKC) is a key enzyme in regulating a variety of cellular functions. PKC, is the most abundant PKC isoform expressed in skeletal muscle. However, the functional role of PKC, linked to muscle regeneration has not yet been identified. Using reverse transcription (RT)-PCR and immunofluorescence analysis, we investigated the expression patterns of PKC, in normal and regenerating tibialis anterior (TA) muscles in the rat. The amount of PKC, mRNA in the muscle increased from the 4th to 6th post-surgical day. Immunofluorescence revealed PKC, protein in quiescent satellite cells identified by c-Met. PKC, immunoreactivity was not observed in many proliferating satellite cells by labeling with BrdU in the regenerating muscle. At 4, 6 and 10 days postsurgery, PKC, immunoreactivity was observed in half the differentiating satellite cells labeling with myogenin. After 4 and 6 days, the localization of PKC, coincided with those of Pax7 and TGF-,. Thus, PKC, may play an important role in inhibiting differentiation and maintaining the quiescent satellite cells in muscle regeneration. [source]

Myogenic precursor cells in craniofacial muscles

ORAL DISEASES, Issue 2 2007
LK McLoon
Craniofacial skeletal muscles (CskM), including the masticatory (MM), extraocular (EOM) and laryngeal muscles (LM), have a number of properties that set them apart from the majority of skeletal muscles (SkM). They have embryological origins that are distinct from musculature elsewhere in the body, they express a number of immature myosin heavy chain isoforms and maintain increased and distinct expression of a number of myogenic growth factors and their receptors from other adult SkMs. Furthermore, it has recently been demonstrated that unlike limb SkM, normal adult EOM and LM retain a population of activated satellite cells, the regenerative cell in adult SkM. In order to maintain this proliferative pool throughout life, CSkM may contain more satellite cells and/or more multipotent precursor cells that may be more resistant to apoptosis than those found in limb muscle. A further exciting question is whether this potentially more active muscle precursor cell population could be utilized not only for SkM repair, but be harnessed for repair or reconstruction of other tissues, such as nervous tissue or bone. This is a highly attractive speculation as the innate regenerative capacity of craniofacial muscles would ensure the donor tissue would not have compromised future function. [source]

IFN-, gene therapy by intrasplenic hepatocyte transplantation: a novel strategy for reversing hepatic fibrosis in Schistosoma japonicum -infected mice

PARASITE IMMUNOLOGY, Issue 1 2001
Lihuang Zhang
Liver-targeted gene therapy using hepatocyte as recipient cells has recently been documented to be effective in treatment of numerous hepatic diseases, such as metabolic diseases and liver carcinoma. IFN-, elicits antipreliferative and antifibrogenic activity in a variety of mesenchymal cells, including hepatic satellite cells. To investigate the antifibrogenic response of liver gene therapy mediated by intrasplenic transplantation of gene-modified hepatocytes, normal mouse liver cell line BNL CL.2 cells were transfected with murine IFN-, gene (BNL.IFN-,) in vitro, and transplanted intrasplenically into Schistosoma japonicum -infected mice. The amounts and distribution of IFN-, (which inhibits collagen synthesis), TGF-, (which stimulates collagen synthesis) and extracellular matrix, including type I and III collagen, were detected. In mice infected with S. japonicum and then treated with BNL.IFN-,, an increase of IFN-, and decrease of TGF-,1 were detected at 20 weeks postinfection compared to untreated S. japonicum -infected mice. Immunohistochemical analysis showed that S. japonicum infection induced a marked increase of type I and III collagen synthesis. Whereas, 4 weeks after treatment with BNL.IFN-,, net synthesis rates of type I and III collagen were markedly decreased in the liver of infected mice. In addition, a decreased expression of TGF-,1 and its receptor TGF-,RII in the liver of BNL.IFN-,-treated mice was also observed. Moreover, the decrease in TGF-,1 and TGF-,RII protein approximately paralleled the decrease in their mRNA expression, which was detected by RNA dot blotting. The data indicate that intrasplenic transplantation of IFN-, gene-modified hepatocyte can be a candidate approach to treat hepatic fibrosis. [source]

Melatonin is as Effective as Testosterone in the Prevention of Soleus Muscle Atrophy Induced by Castration in Rats

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2008
Jale Öner
Abstract The purpose of this experiment was to compare the weight, insulin-like growth factor-I (IGF-I) expression, and ultrastructure of the soleus muscle in growing castrated rats treated with testosterone or melatonin. In this study, adult male Wistar albino rats were used. The groups were arranged as sham, castrated, and testosterone- or melatonin-injected groups after castration. The soleus muscle samples were fixed in Bouin's solution for immunohistochemistry, and in 2.5% gluteraldehyde in 0.1 M phosphate buffer (pH 7.4). Whereas castration reduced the soleus weight and fiber diameter, testosterone and melatonin administration increased them. IGF-I immunostaining observed in the satellite cells and periphery of the myofibers was least intense in the castrated group. Strong staining of IGF-I was observed in the testosterone- and melatonin-administered groups. The ultrastructure of the soleus muscle in castrated animals showed the important ultrastructural modifications related to degeneration. In these groups, degenerative mitochondria, glycogen clusters under the sarcolemma, irregular Z lines, and loss of lamina externa were observed. The ultrastructure of myofibrils in the testosterone- and melatonin-injected groups was similar to that in sham groups in view of structure. In conclusion, we suggest that melatonin is as effective as testosterone in the prevention of atrophy induced by castration through the IGF-I axis. Anat Rec, 291:448,455, 2008. © 2008 Wiley-Liss, Inc. [source]

Co-expression of IGF-1 family members with myogenic regulatory factors following acute damaging muscle-lengthening contractions in humans

THE JOURNAL OF PHYSIOLOGY, Issue 22 2008
Bryon R. McKay
Muscle regeneration following injury is dependent on the ability of muscle satellite cells to activate, proliferate and fuse with damaged fibres. This process is controlled by the myogenic regulatory factors (MRF). Little is known about the temporal relation of the MRF with the expression of known myogenic growth factors (i.e. IGF-1) in humans following muscle damage. Eight subjects (20.6 ± 2.1 years; 81.4 ± 9.8 kg) performed 300 lengthening contractions (180 deg s,1) of their knee extensors in one leg on a dynamometer. Blood and muscle samples were collected before and at 4 (T4), 24 (T24), 72 (T72) and 120 h (T120) post-exercise. Mechano growth factor (MGF), IGF-1Ea and IGF-1Eb mRNA were quantified. Serum IGF-1 did not change over the post-exercise time course. IGF-1Ea and IGF-1Eb mRNA increased ,4- to 6-fold by T72 (P < 0.01) and MGF mRNA expression peaked at T24 (P= 0.005). MyoD mRNA expression increased ,2-fold at T4 (P < 0.05). Myf5 expression peaked at T24 (P < 0.05), while MRF4 and myogenin mRNA expression peaked at T72 (P < 0.05). Myf5 expression strongly correlated with the increase in MGF mRNA (r2= 0.83; P= 0.03), while MRF4 was correlated with both IGF-1Ea and -Eb (r2= 0.90; r2= 0.81, respectively; P < 0.05). Immunofluorescence analysis showed IGF-1 protein expression localized to satellite cells at T24, and to satellite cells and the myofibre at T72 and T120; IGF-1 was not detected at T0 or T4. These results suggest that the temporal response of MGF is probably related to the activation/proliferation phase of the myogenic programme as marked by an increase in both Myf5 and MyoD, while IGF-1Ea and - Eb may be temporally related to differentiation as marked by an increase in MRF4 and myogenin expression following acute muscle damage. [source]

In vitro measurement of post-natal changes in proliferating satellite cell frequency during rat muscle growth

Mechano-biology of skeletal muscle hypertrophy and regeneration: Possible mechanism of stretch-induced activation of resident myogenic stem cells

ANIMAL SCIENCE JOURNAL, Issue 1 2010
Ryuichi TATSUMI
ABSTRACT In undamaged postnatal muscle fibers with normal contraction and relaxation activities, quiescent satellite cells of resident myogenic stem cells are interposed between the overlying external lamina and the sarcolemma of a subjacent mature muscle fiber. When muscle is injured, exercised, overused or mechanically stretched, these cells are activated to enter the cell proliferation cycle, divide, differentiate, and fuse with the adjacent muscle fiber, and are responsible for regeneration and work-induced hypertrophy of muscle fibers. Therefore, a mechanism must exist to translate mechanical changes in muscle tissue into chemical signals that can activate satellite cells. Recent studies of satellite cells or single muscle fibers in culture and in vivo demonstrated the essential role of hepatocyte growth factor (HGF) and nitric oxide (NO) radical in the activation pathway. These experiments have also reported that mechanically stretching satellite cells or living skeletal muscles triggers the activation by rapid release of HGF from its extracellular tethering and the subsequent presentation to the receptor c-met. HGF release has been shown to rely on calcium-calmodulin formation and NO radical production in satellite cells and/or muscle fibers in response to the mechanical perturbation, and depend on the subsequent up-regulation of matrix metalloproteinase (MMP) activity. These results indicate that the activation mechanism is a cascade of events including calcium ion influx, calcium-calmodulin formation, NO synthase activation, NO radical production, MMP activation, HGF release and binding to c-met. Better understanding of ,mechano-biology' on the satellite cell activation is essential for designing procedures that could enhance muscle growth and repair activities in meat-animal agriculture and also in neuromuscular disease and aging in humans. [source]

A cellular model system of differentiated human myotubes,

APMIS, Issue 11 2001
M. GASTER
The aim of this study was to select an effective and stable protocol for the differentiation of human satellite cells (Sc) and to identify the optimal time period for the experimental use of differentiated human Sc-cultures. In order to identify the differentiation conditions which give a good survival of myotubes and a high grade of differentiation, Sc-cultures were induced to differentiate in media supplemented with either 2% fetal calf serum (FCS) 2% horse serum (HS) or 10% HS. Based on higher CK-activities in cultures differentiating in FCS-supplemented media compared to horse sera, fetal calf serum was chosen to induce differentiation. The ATP, DNA and protein content increased during the first 4 days after induction of differentiation and was followed by a period with minor changes. The maximal differences of ATP, DNA and protein between days 4,10 were evaluated and the differences in the three components were found to be less than 20% of the average value with a certainity of more than 0.9. Day 8-myotubes were investigated morphologically and were found immunoreactive for fast myosin, and expressed areas with clear cross striation. We recommend the use of differentiated Sc-cultures in the period from day 4 to 8 after induction of differentiation as only minor differentation-related changes will take place in the cells during this period of time. [source]

Expression and localization of opioid receptors in muscle satellite cells: no difference between fibromyalgia patients and healthy subjects

ARTHRITIS & RHEUMATISM, Issue 11 2003
Souzan Salemi PhD
No abstract is available for this article. [source]

Differentiation rather than aging of muscle stem cells abolishes their telomerase activity

BIOTECHNOLOGY PROGRESS, Issue 4 2009
Matthew S. O'Connor
Abstract A general feature of stem cells is the ability to routinely proliferate to build, maintain, and repair organ systems. Accordingly, embryonic and germline, as well as some adult stem cells, produce the telomerase enzyme at various levels of expression. Our results show that, while muscle is a largely postmitotic tissue, the muscle stem cells (satellite cells) that maintain this biological system throughout adult life do indeed display robust telomerase activity. Conversely, primary myoblasts (the immediate progeny of satellite cells) quickly and dramatically downregulate telomerase activity. This work thus suggests that satellite cells, and early transient myoblasts, may be more promising therapeutic candidates for regenerative medicine than traditionally utilized myoblast cultures. Muscle atrophy accompanies human aging, and satellite cells endogenous to aged muscle can be triggered to regenerate old tissue by exogenous molecular cues. Therefore, we also examined whether these aged muscle stem cells would produce tissue that is "young" with respect to telomere maintenance. Interestingly, this work shows that the telomerase activity in muscle stem cells is largely retained into old age wintin inbred "long" telomere mice and in wild-derived short telomere mouse strains, and that age-specific telomere shortening is undetectable in the old differentiated muscle fibers of either strain. Summarily, this work establishes that young and old muscle stem cells, but not necessarily their progeny, myoblasts, are likely to produce tissue with normal telomere maintenance when used in molecular and regenerative medicine approaches for tissue repair. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]