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.

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

“…HBO therapy reduced production of inflammatory cytokines and macrophage chemokines following crush injury; when administered with AFMSCs, HBO reduced apoptosis of AFMSCs in comparison to AFMSCs alone; myelination and motor recovery superior in HBO + AFMSC group Pan et al [110] Rat sciatic crush U Fibrin glue…”

“…Survival of AFDSCs following transplantation can be limited and as a result, efforts have been made to improve in vivo survivability. Inhibition of inflammatory mediators can attenuate the apoptotic cascade [110][111][112] . Cells can be genetically modified in order to over-express therapeutic genes.…”

Practical considerations concerning the use of stem cells for peripheral nerve repair

“…Survival and effectiveness of transplanted cells can be improved by ex vivo genetic manipulation or concomitant delivery of protective agents or trophic factors. Pan and colleagues 45 found that administration of granulocyte-colony stimulating factor to animals receiving transplants of amniotic fluid mesenchymal stem cells not only improved survival of transplanted cells but also augmented nerve regeneration over that of a primarily cell-based approach. Additionally, differences in the material in which stem cells are delivered have demonstrated varying capacities to support long-term cell survival.…”

Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration

“…The short-term survival of implanted stem cells might diminish cell transplantation-mediated beneficial effects. The increased survival of implanted cells could be augmented by the suppression of inflammatory cytokines through the inhibition of inflammatory cell deposits [23]. Therefore, the present study was designed to evaluate whether a combination of HBO and AFS transplantation could augment peripheral nerve regeneration.…”