title: Combination of G-CSF administration and human amniotic fluid mesenchymal stem cell transplantation promotes peripheral nerve regeneration.
abstract: Amniotic fluid mesenchymal stem cells (AFS) harbor the potential to improve peripheral nerve injury by inherited neurotrophic factor secretion, but present the drawback of the short-term survival after transplantation. Granulocyte-colony stimulating factor (G-CSF) has a diversity of functions, including anti-inflammatory and anti-apoptotic effects. This study was conducted to evaluate whether G-CSF could augment the neuroprotective effect of transplanted AFS against peripheral nerve injury. The potential involvement of anti-inflammation/anti-apoptosis effect was also investigated. Peripheral nerve injury was produced in Sprauge-Dawley rats by crushing left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. G-CSF (50 microg/kg) was administrated by intra-peritoneal injection for 7 consecutive days. Cell apoptosis, inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. Crush injury induced inflammatory response, disrupted nerve integrity, and impaired nerve function in sciatic nerve. Crush injury-provoked inflammation was attenuated in groups receiving G-CSF but not in AFS only group. In transplanted AFS, marked apoptosis was detected and this event was reduced by G-CSF treatment. Increased nerve myelination and improved motor function were observed in AFS transplanted, G-CSF administrated, and AFS/G-CSF combined treatment groups. Significantly, the combined treatment showed the most beneficial effect. In conclusion, the concomitant treatment of AFS with G-CSF augments peripheral nerve regeneration which may involve the suppression of apoptotic death in implanted AFS and the attenuation of inflammatory response.
authors.affiliation: Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan. hcpan2003@yahoo.com.tw
authors.forename: Hung-Chuan
authors.initials: HC
authors.lastname: Pan
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Fu-Chou
authors.initials: FC
authors.lastname: Cheng
authors.forename: Shu-Pen
authors.initials: SP
authors.lastname: Ho
authors.forename: Mu-Jung
authors.initials: MJ
authors.lastname: Liu
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Chang
authors.forename: Yeou-Chih
authors.initials: YC
authors.lastname: Wang
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D045164:Mesenchymal Stem Cell Transplantation; D009409:Nerve Crush; D009416:Nerve Regeneration; D009431:Neural Conduction; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor