Granulocyte-colony stimulating factor enhances muscle proliferation and strength following skeletal muscle injury in rats

Author:

Stratos Ioannis,Rotter Robert,Eipel Christian,Mittlmeier Thomas,Vollmar Brigitte

Abstract

Insufficiency of skeletal muscle regeneration often impedes the healing process with functional deficiencies and scar formation. We tested the hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) with respect to its efficacy to improve functional muscle regeneration following skeletal muscle injury in Wistar rats. After crush injury to the left soleus muscle, animals received daily G-CSF (20 μg/kg ip) or vehicle solution ( n = 30 per group each). Sham-operated animals without muscle injury served as controls ( n = 15). After in vivo assessment of the fast-twitch and tetanic contraction capacity of the soleus muscles at days 4, 7, and 14 post-injury, sampling of muscle tissue served for analysis of satellite cell proliferation [bromodeoxyuridine (BrdU)/laminin and BrdU/desmin double immunohistochemistry] and cell apoptosis (transferase nick-end labeling analysis). Muscle strength analysis revealed recovery of contraction forces to 26 ± 2, 35 ± 3, and 53 ± 3% (twitch force) and to 20 ± 3, 24 ± 2, and 37 ± 2% (tetanic force) within the 14-day observation period in vehicle-treated animals. In contrast, G-CSF increased contractile forces with markedly higher values at day 7 (twitch force: 42 ± 2%; tetanic force: 34 ± 2%) and day 14 (twitch force: 62 ± 3%; tetanic force: 43 ± 3%). This enhancement of muscle function was preceded by a significant increase of satellite cell proliferation (BrdU-positive cells/mm2: 27 ± 6 vs. vehicle: 12 ± 3) and a moderate decrease of cell apoptosis (transferase nick-end labeling-positive cells/mm2: 11 ± 2 vs. vehicle: 16 ± 3) at day 4. In conclusion, G-CSF histologically promoted viability and proliferation of muscle cells and functionally enhanced recovery of muscle strength. Thus G-CSF might represent a therapeutic option to optimize the posttraumatic course of muscle tissue healing.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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