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Combination of G-CSF Administration and Human Amniotic Fluid Mesenchymal Stem Cell Transplantation Promotes Peripheral Nerve Regeneration

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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 μg/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.

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Acknowledgements

This study was supported by grants from TCVGH-964906D and NSC 96–2314-B-075A-001, Taiwan. This statistical analysis is supported by the biostatistics task force of Taichung Veterans General Hospital, Taiwan, ROC.

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Authors and Affiliations

  1. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan

    Hung-Chuan Pan & Mu-Jung Liu

  2. Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan

    Hung-Chuan Pan & Chung-Jung Chen

  3. Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan

    Hung-Chuan Pan & Shu-Pen Ho

  4. Stem Cell Center, Taichung Veterans General Hospital, Taichung, Taiwan

    Fu-Chou Cheng

  5. Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan

    Shiaw-Min Hwang

  6. Department of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan

    Ming-Hong Chang

  7. Department of Neurosurgery, Chung-Shan Medical University Hospital, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, 402, Taiwan, ROC

    Yeou-Chih Wang

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  1. Hung-Chuan Pan
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Correspondence to Yeou-Chih Wang.

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Pan, HC., Chen, CJ., Cheng, FC. et al. Combination of G-CSF Administration and Human Amniotic Fluid Mesenchymal Stem Cell Transplantation Promotes Peripheral Nerve Regeneration. Neurochem Res 34, 518–527 (2009). https://doi.org/10.1007/s11064-008-9815-5

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  • DOI: https://doi.org/10.1007/s11064-008-9815-5

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