TY - JOUR

T1 - The breaking and making of healthy adult human skeletal muscle in vivo

AU - Mackey, Abigail L.

AU - Kjaer, Michael

PY - 2017

Y1 - 2017

N2 - BackgroundWhile muscle regeneration has been extensively studied in animal and cell culture models, in vivo myogenesis in adult human skeletal muscle has not been investigated in detail.MethodsUsing forced lengthening contractions induced by electrical stimulation, we induced myofibre injury in young healthy males. Muscle biopsies were collected from the injured leg 7 and 30 days after muscle injury and from the uninjured leg as a control. Immuno-stained single muscle fibres and muscle cross sections were studied by wide-field and confocal microscopy. Samples were also studied at the ultra-structural level by electron microscopy.ResultsMicroscopy of single muscle fibres in 3 dimensions revealed a repeating pattern of necrotic and regenerating zones along the length of the same myofibre, characterised by extensive macrophage infiltration alongside differentiating myogenic progenitor cells and myotubes: the hallmarks of myogenesis. The myofibre basement membrane was preserved during these processes and interestingly was seen at a later stage as a second basement membrane surrounding the regenerating fibres.ConclusionsThis is the first work to document in vivo myogenesis in humans in detail and highlights the importance of the basement membrane in the process of regeneration. In addition, it provides insight into parallels between the regeneration of adult skeletal muscle in mouse and man, confirming that this model may be a useful tool in investigating myofibre and matrix formation, as well as specific cell types, during regeneration from the perspective of human muscle.

AB - BackgroundWhile muscle regeneration has been extensively studied in animal and cell culture models, in vivo myogenesis in adult human skeletal muscle has not been investigated in detail.MethodsUsing forced lengthening contractions induced by electrical stimulation, we induced myofibre injury in young healthy males. Muscle biopsies were collected from the injured leg 7 and 30 days after muscle injury and from the uninjured leg as a control. Immuno-stained single muscle fibres and muscle cross sections were studied by wide-field and confocal microscopy. Samples were also studied at the ultra-structural level by electron microscopy.ResultsMicroscopy of single muscle fibres in 3 dimensions revealed a repeating pattern of necrotic and regenerating zones along the length of the same myofibre, characterised by extensive macrophage infiltration alongside differentiating myogenic progenitor cells and myotubes: the hallmarks of myogenesis. The myofibre basement membrane was preserved during these processes and interestingly was seen at a later stage as a second basement membrane surrounding the regenerating fibres.ConclusionsThis is the first work to document in vivo myogenesis in humans in detail and highlights the importance of the basement membrane in the process of regeneration. In addition, it provides insight into parallels between the regeneration of adult skeletal muscle in mouse and man, confirming that this model may be a useful tool in investigating myofibre and matrix formation, as well as specific cell types, during regeneration from the perspective of human muscle.

U2 - 10.1186/s13395-017-0142-x

DO - 10.1186/s13395-017-0142-x

M3 - Journal article

C2 - 29115986

VL - 7

JO - Skeletal Muscle

JF - Skeletal Muscle

SN - 2044-5040

M1 - 24

ER -