Variability of hip muscle volume determined by computed tomography

Muscle volume is an essential parameter in clinical evaluation and in biomechanical model development. Nevertheless, the difficulty in volumic muscle reconstruction from medical images is the noise they contain that limits the efficiency of image processing to automatically segment muscle. This study was conducted to explore hip muscle volume from CT-scan acquisition and to analyze the variability of muscle volume for a population of 98 subjects with age ranged from 21 to 94 years. To obtain three-dimensional muscle reconstruction, a method based on a deformation of a parametric specific object generated from a reduced number of muscle contours was used. A reproducibility study was conducted for muscle volume estimation. Coefficient of variation was found less than 8.9% and intraclass correlation coefficients were greater than 0.88. Results showed no significant difference between left and right muscles for this population. After adjustment to age and body mass index, hip muscle volumes were significantly different between men and women. This muscle volume reconstruction method allowed quantifying muscle volume distribution within a large population.     

Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages

Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal beta III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders.     

Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles

Satellite cells reside beneath the basal lamina of skeletal muscle fibers and include cells that act as precursors for muscle growth and repair. Although they share a common anatomical localization and typically are considered a homogeneous population, satellite cells actually exhibit substantial heterogeneity. We used cell-surface marker expression to purify from the satellite cell pool a distinct population of skeletal muscle precursors (SMPs) that function as muscle stem cells. When engrafted into muscle of dystrophin-deficient mdx mice, purified SMPs contributed to up to 94% of myofibers, restoring dystrophin expression and significantly improving muscle histology and contractile function. Transplanted SMPs also entered the satellite cell compartment, renewing the endogenous stem cell pool and participating in subsequent rounds of injury repair. Together, these studies indicate the presence in adult skeletal muscle of prospectively isolatable muscle-forming stem cells and directly demonstrate the efficacy of myogenic stem cell transplant for treating muscle degenerative disease.     

Fgf8 drives myogenic progression of a novel lateral fast muscle fibre population in zebrafish

Fibroblast growth factors (Fgfs) have long been implicated in regulating vertebrate skeletal muscle differentiation, but their precise role(s) in vivo remain unclear. Here, we show that Fgf8 signalling in the somite is required for myod expression and terminal differentiation of a subset of fast muscle cells in the zebrafish lateral somite. In the absence of Fgf8, lateral somite cells transiently express myf5 but fail to make muscle and remain in a dermomyotome-like state characterised by pax3 and meox expression. Slow muscle fibres form and commence normal migration in the absence of Fgf8, but fail to traverse the expanded undifferentiated lateral somite. The Fgf8-independent residual population of medial fast muscle fibres is not Hedgehog dependent. However, Fgf8-independent medial fast muscle precursors are lacking in floatinghead mutants, suggesting that they require another ventral midline-derived signal. We conclude that Fgf8 drives terminal differentiation of a specific population of lateral muscle precursor cells within the early somite.     

Reduced sexual dimorphism in upper arm muscle circumference associated with protein-deficient diet in a South American population

Animal experiments have demonstrated that individuals exhibit differing tendencies to arrest growth and resorb muscle tissue under nutritional stress. Since placental and adrenocortical hormones are active in promoting muscle tissue resorption, sex differences may exist. In order to identify such sex differences, the upper arm circumferences of 362 individuals, aged one to 60 years, living in an area of chronic protein-calorie malnutrition were compared by age and sex with published data collected from U.S. and highland Peruvian populations. Sexual dimorphism for arm muscle circumference in the malnourished population is less than in U.S. samples of comparable age-categories. The highland population is closer to U.S. samples in the degree of dimorphism. The reduction in muscle circumference of males in the malnourished population appears to be the cause of the comparatively greater similarity of the sexes where protein-calorie malnutrition is experienced from infancy through adolescence. High muscle relief and excellent tonus in these same males indicate that reduced muscle circumference is not the result of flaccidity or higher ratios of compressible fat to muscle tissue. Reduction of muscle tissue in undernourished males is a reduction in total metabolic demand. Such reductions are adaptive in areas of chronic nutritional stress.     

Finite element modeling of aponeurotomy: altered intramuscular myofascial force transmission yields complex sarcomere length distributions determining acute effects

Finite element modeling of aponeurotomized rat extensor digitorium longus muscle was performed to investigate the acute effects of proximal aponeurotomy. The specific goal was to assess the changes in lengths of sarcomeres within aponeurotomized muscle and to explain how the intervention leads to alterations in muscle length-force characteristics. Major changes in muscle length-active force characteristics were shown for the aponeurotomized muscle modeled with (1) only a discontinuity in the proximal aponeurosis and (2) with additional discontinuities of the muscles' extracellular matrix (i.e., when both myotendinous and myofascial force transmission mechanisms are interfered with). After muscle lengthening, two cut ends of the aponeurosis were separated by a gap. After intervention (1), only active slack length increased (by approximately 0.9 mm) and limited reductions in muscle active force were found (e.g., muscle optimum force decreased by only 1%) After intervention (2) active slack increased further (by 1.2 mm) and optimum length as well (by 2.0 mm) shifted and the range between these lengths increased. In addition, muscle active force was reduced substantially (e.g., muscle optimum force decreased by 21%). The modeled tearing of the intramuscular connective tissue divides the muscle into a proximal and a distal population of muscle fibers. The altered force transmission was shown to lead to major sarcomere length distributions [not encountered in the intact muscle and after intervention (1)], with contrasting effects for the two muscle fiber populations: (a) Within the distal population (i.e. fibers with no myotendinous connection to the muscles' origin), sarcomeres were much shorter than within the proximal population (fibers with intact myotendinous junction at both ends). (b) Within the distal population, from proximal ends of muscle fibers to distal ends, the serial distribution of sarcomere lengths ranged from the lowest length to high lengths. In contrast within the proximal population, the direction of the distribution was reversed. Such differences in distribution of sarcomere lengths between the proximal and distal fiber populations explain the shifts in muscle active slack and optimal lengths. Muscle force reduction after intervention (2) is explained primarily by the short sarcomeres within the distal population. However, fiber stress distributions showed contribution of the majority of the sarcomeres to muscle force: myofascial force transmission prevents the sarcomeres from shortening to nonphysiological lengths. It is concluded that interfering with the intramuscular myofascial force transmission due to rupturing of the intramuscular connective tissue leads to a complex distribution of sarcomere lengths within the aponeurotomized muscle and this determines the acute effects of the intervention on muscle length-force characteristics rather than the intervention with the myotendinous force transmission after which the intervention was named. These results suggest that during surgery, but also postoperatively, major attention should be focused on the length and activity of aponeurotomized muscle, as changes in connective tissue tear depth will affect the acute effects of the intervention.     

Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration

Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell-mediated therapies.     

Interpretation of Tracer Washout Curves from a Population of Muscle Fibers

Consideration is given to the role of a population of muscle fibers of distributed diameters in the observed washout of a tracer, with particular reference to radioisotopic K and muscle fibers. It is concluded that if washout of tracer from a single fiber is described as first order, then washout of tracer from a population of fibers is apt to appear as first order.     

Bmi1 is expressed in postnatal myogenic satellite cells, controls their maintenance and plays an essential role in repeated muscle regeneration

Satellite cells are the resident stem cell population of the adult mammalian skeletal muscle and they play a crucial role in its homeostasis and in its regenerative capacity after injury. We show here that the Polycomb group (PcG) gene Bmi1 is expressed in both the Pax7 positive (+)/Myf5 negative (-) stem cell population as well as the Pax7+/Myf5+ committed myogenic progenitor population. Depletion of Pax7+/Myf5- satellite cells with reciprocal increase in Pax7+/Myf5+ as well as MyoD positive (+) cells is seen in Bmi1-/- mice leading to reduced postnatal muscle fiber size and impaired regeneration upon injury. Bmi1-/- satellite cells have a reduced proliferative capacity and fail to re-enter the cell cycle when stimulated by high serum conditions in vitro, in keeping with a cell intrinsic defect. Thus, both the in vivo and in vitro results suggest that Bmi1 plays a crucial role in the maintenance of the stem cell pool in postnatal skeletal muscle and is essential for efficient muscle regeneration after injury especially after repeated muscle injury.     

Distribution of muscle fibers in skeletal muscles of the cheetah (Acinonyx jubatus)

We examine the muscle fiber population of skeletal muscles from whole body in the cheetah (Acinonyx jubatus). In the present experiments, we showed the characteristics of fiber composition in the cheetah by comparative studies among the cheetah, domestic cat, and the beagle dog. Fiber population was determined on muscle fibers stained with monoclonal antibody to each myosin heavy chain isoform. Histochemical analysis demonstrated that many muscles in the cheetah and domestic cat had a low percentage of Type I fibers and a high percentage of Type IIx fibers, while those in the beagle dog showed a high percentage of Type IIa. The hindlimb muscles in the cheetah had a higher percentage of Type II (Type IIa + IIx) fiber than the forelimb muscles. This fact suggests that the propulsive role of the hindlimb is greater than the forelimb in the cheetah. The longissimus in the cheetah had a high percentage of Type IIx fibers over a wide range from the thoracic to lumbar parts, while the population of muscle fibers in this muscle was different depending on the parts in the domestic cat and beagle dog. This indicates that the cheetah can produce a strong and quick extension of the spinal column and increase its stiffness during locomotion. Furthermore, we found the notable difference of muscle fiber type population between flexors and extensors of digits in the cheetah. The present experiments show the characteristics of muscle fibers in the cheetah, corresponded to its ability to perform high-speed running.     

Correlation between mechanical and enzymatic events in contracting skeletal muscle fiber

The conventional hypothesis of muscle contraction postulates that the interaction between actin and myosin involves tight coupling between the power stroke and hydrolysis of ATP. However, some in vitro experiments suggested that hydrolysis of a single molecule of ATP caused multiple mechanical cycles. To test whether the tight coupling is present in contracting muscle, we simultaneously followed mechanical and enzymatic events in a small population of cross-bridges of glycerinated rabbit psoas fibers. Such small population behaves as a single cross-bridge when muscle contraction is initiated by a sudden release of caged ATP. Mechanical events were measured by changes of orientation of probes bound to the regulatory domain of myosin. Enzymatic events were simultaneously measured from the same cross-bridge population by the release of fluorescent ADP from the active site. If the conventional view were true, ADP desorption would occur simultaneously with dissociation of cross-bridges from thin filaments and would be followed by cross-bridge rebinding to thin filaments. Such sequence of events was indeed observed in contracting muscle fibers, suggesting that mechanical and enzymatic events are tightly coupled in vivo.     

The potential of muscle stem cells.

Skeletal muscle contains two types of stem cells: satellite cells, which function as myogenic precursors, and a population of multipotent adult stem cells. Satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. An additional stem cell population in adult muscle displays a remarkable capacity to differentiate into hematopoietic cells as well as muscle following transplantation. This article discusses the characteristics and properties of these cell populations, the relationship between them, and the potential for stem cell-based muscle therapeutics.     

Locomotory capacity of Baltic Sea and freshwater populations of the threespine stickleback (Gasterosteus aculeatus)

Two freshwater populations and one marine population (Baltic Sea) of threespine stickeback (Gasterosteus aculeatus) from Northeastern Germany were studied with regard to locomotory capacity: sustained swimming performance, activities of key enzymes in axial muscle, pectoral fin muscle and heart, and morphology. We postulated that life history differences between migratory Baltic Sea and resident freshwater populations could have led to a divergence in their locomotory capacity. The activity of citrate synthase (CS) in pectoral muscle correlated with critical swimming speed. Critical swimming speed, aerobic and anaerobic capacity of the pectoral fin muscle were population-specific. The Baltic Sea sticklebacks had a higher locomotory capacity (activity of CS in pectoral muscle, critical swimming speed) than sticklebacks of one freshwater population. However, another freshwater population expressed a similar locomotory capacity as the Baltic Sea population. In addition, Baltic Sea sticklebacks had a greater mass and lower anaerobic capacity of the pectoral fin muscle than the freshwater sticklebacks. The results are interpreted as an indication of a proceeding divergence between marine and resident freshwater populations and between freshwater populations of G. aculeatus originating from marine ancestors. The migratory Baltic Sea sticklebacks had better morphological prerequisites for sustained swimming than both freshwater populations, but there was no general difference in the locomotory capacity between marine and freshwater sticklebacks. However, their morphology could favour a more effective locomotion in the Baltic Sea sticklebacks.     

A study of the muscle force waveform using a population stochastic model of skeletal muscle

A population stochastic model based on the differing properties and the independent activation of motor units is used to describe the production of force in the contracting skeletal muscle. Detailed force predictions of the model concerning a hand muscle are obtained by computer simulation. General features of the force signal are established analyticaly on the basis of the general properties of the neuromuscular system which the population model takes into account. The results show that the asynchronous activity of motor units and the distribution of their filtering and firing properties at various levels of muscle contraction are esponsible, at least partially, for the main features of the muscle force waveform, including tremor.     

Isolation and characterization of cells with neurogenic potential from adult skeletal muscle

Autologous cell therapies in neurodegenerative diseases and stroke will require an efficient generation of neuroprogenitors or neurons. We have previously shown that presumptive neural progenitors can be obtained from a candidate stem cell population isolated from adult skeletal muscle. Here we describe experimental conditions to isolate and characterize the cells with neurogenic potential from this population. Candidate stem cell population was isolated from adult skeletal muscle and expanded for selection during at least 30 cell divisions. FACS analysis revealed that this population was homogeneous with respect to CD45 (-), CD34 (-), and heterogeneous for CD90 (Thy-1) expression. The population was separated by cell sorting into three sub-populations based on CD90 expression (CD90-, CD90+, and CD90++) and each population expanded rapidly as free-floating spheres. When dissociated and plated in a neuronal differentiation medium, a large number of CD90+ cells acquired morphological characteristics of neuroprogenitors and neurons, and expressed markers of neurons but no markers of glial or muscle cells. In contrast, CD90- and CD90++ cells lacked this ability. Comparison of CD90+ and CD90- populations may be useful for studying the molecular characteristics defining the neuronal potential of stem cells from adult muscle. The selection of CD90+ expressing cells, combined with the growth conditions presented here, allows for rapid generation of a large number of cells which may be useful for autologous cell replacement therapies in the central nervous system.     

Modulation of human muscle spindle discharge by arterial pulsations--functional effects and consequences

Arterial pulsations are known to modulate muscle spindle firing; however, the physiological significance of such synchronised modulation has not been investigated. Unitary recordings were made from 75 human muscle spindle afferents innervating the pretibial muscles. The modulation of muscle spindle discharge by arterial pulsations was evaluated by R-wave triggered averaging and power spectral analysis. We describe various effects arterial pulsations may have on muscle spindle afferent discharge. Afferents could be "driven" by arterial pulsations, e.g., showing no other spontaneous activity than spikes generated with cardiac rhythmicity. Among afferents showing ongoing discharge that was not primarily related to cardiac rhythmicity we illustrate several mechanisms by which individual spikes may become phase-locked. However, in the majority of afferents the discharge rate was modulated by the pulse wave without spikes being phase locked. Then we assessed whether these influences changed in two physiological conditions in which a sustained increase in muscle sympathetic nerve activity was observed without activation of fusimotor neurones: a maximal inspiratory breath-hold, which causes a fall in systolic pressure, and acute muscle pain, which causes an increase in systolic pressure. The majority of primary muscle spindle afferents displayed pulse-wave modulation, but neither apnoea nor pain had any significant effect on the strength of this modulation, suggesting that the physiological noise injected by the arterial pulsations is robust and relatively insensitive to fluctuations in blood pressure. Within the afferent population there was a similar number of muscle spindles that were inhibited and that were excited by the arterial pulse wave, indicating that after signal integration at the population level, arterial pulsations of opposite polarity would cancel each other out. We speculate that with close-to-threshold stimuli the arterial pulsations may serve as an endogenous noise source that may synchronise the sporadic discharge within the afferent population and thus facilitate the detection of weak stimuli.     

A new look at the origin, function, and "stem-cell" status of muscle satellite cells

Muscle satellite cells have long been considered a distinct myogenic lineage responsible for postnatal growth, repair, and maintenance of skeletal muscle. Recent studies in mice, however, have revealed the potential for highly purified hematopoietic stem cells from bone marrow to participate in muscle regeneration. Perhaps more significantly, a population of putative stem cells isolated directly from skeletal muscle efficiently reconstitutes the hematopoietic compartment and participates in muscle regeneration following intravenous injection in mice. The plasticity of muscle stem cells has raised important questions regarding the relationship between the muscle-derived stem cells and the skeletal muscle satellite cells. Furthermore, the ability of hematopoietic cells to undergo myogenesis has prompted new investigations into the embryonic origin of satellite cells. Recent developmental studies suggest that a population of satellite cells is derived from progenitors in the embryonic vasculature. Taken together, these studies provide the first evidence that pluripotential stem cells are present within adult skeletal muscle. Tissue-specific stem cells, including satellite cells, may share a common embryonic origin and possess the capacity to activate diverse genetic programs in response to environmental stimuli. Manipulation of such tissue-specific stem cells may eventually revolutionize therapies for degenerative diseases, including muscular dystrophy.     

Lumped and population stochastic models of skeletal muscle: Implications and predictions

Lumped models of skeletal muscle have been assumed a) in the design of experiments and the interpretation of experimental findings, b) in theoretical studies. In this paper, a population model that takes into account the differing properties and separate (independent) activation of motor units is presented as the most appropriate for muscle. A realistic (for muscle) transformation, populationlumped model, resulting in the lumping of motor unit neural signals or system responses, is proposed. On this basis, the possibility of modelling muscle as a single system is examined; and the consequences of treating muscle as a lumped system, in experiments or theoretical studies, are discussed. Also, the advantages of lumping, in models of muscle, are reviewed. Predictions of a computer population model, together with actual recordings from a hand muscle, are used to confirm the results of the analysis.