title: Granulocyte-colony stimulating factor enhances muscle proliferation and strength following skeletal muscle injury in rats.
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 mug/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/mm(2): 27 +/- 6 vs. vehicle: 12 +/- 3) and a moderate decrease of cell apoptosis (transferase nick-end labeling-positive cells/mm(2): 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.
authors: Inst. for Experimental Surgery, Univ. of Rostock, Schillingallee 69a, 18055 Rostock, Germany.
authors: Ioannis
authors: I
authors: Stratos
authors: Robert
authors: R
authors: Rotter
authors: Christian
authors: C
authors: Eipel
authors: Thomas
authors: T
authors: Mittlmeier
authors: Brigitte
authors: B
authors: Vollmar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D009135:Muscular Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D012038:Regeneration / Q000187:drug effects*; D012107:Research Design; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D003402:Creatine Kinase