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1 Institute for Experimental Surgery, University of Rostock, Germany
2 Department of Trauma and Reconstructive Surgery, University of Rostock, Germany
* To whom correspondence should be addressed. E-mail: brigitte.vollmar{at}med.uni-rostock.de.
Insufficiency of skeletal muscle regeneration often impedes the healing process with functional deficiencies and scar formation. We tested the hematopoietic growth 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 i.p.) 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 (TUNEL-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 14d-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 (TUNEL-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.
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