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The efficacy of stem cell-based therapy for neurological diseases depends highly on cell survival post-transplantation. One of the key factors affecting cell survival is the grafting procedure. The current study aims to determine whether needle insertion into intact rat spinal cords creates a hypoxic environment that is prone to lipid peroxidation damage upon reperfusion, and whether an antioxidant protects human neural stem cells (hNSCs) both in vitro and post-transplantation into rat spinal cords. We show here that a single needle injection creates a hypoxic environment within the rat spinal cord that peaks at approximately 12 hours before reperfusion occurs. Lipid peroxidation damage at the transplantation site is evident by 48 hours post-needle insertion. In an in vitro model, hypoxia-reperfusion results in apoptotic death of hNSCs. Pretreatment with the antioxidant, α-lipoic acid, protects hNSCs against hypoxia-reperfusion injury and oxidative stress–mediated cell death. Increasing glutathione, but not Akt signaling, contributes to the protective effect of lipoic acid. Pretreating hNSCs with lipoic acid also increases the cell survival rate 1 month post-transplantation. Further investigation is warranted to develop improved techniques to maximize the survival of transplanted stem cells.
The efficacy of stem cell-based therapy for neurological diseases depends highly on cell survival post-transplantation. One of the key factors affecting cell survival is the grafting procedure. The current study aims to determine whether needle insertion into intact rat spinal cords creates a hypoxic environment that is prone to lipid peroxidation damage upon reperfusion, and whether an antioxidant protects human neural stem cells (hNSCs) both in vitro and post-transplantation into rat spinal cords. We show here that a single needle injection creates a hypoxic environment within the rat spinal cord that peaks at approximately 12 hours before reperfusion occurs. Lipid peroxidation damage at the transplantation site is evident by 48 hours post-needle insertion. In an in vitro model, hypoxia-reperfusion results in apoptotic death of hNSCs. Pretreatment with the antioxidant, α-lipoic acid, protects hNSCs against hypoxia-reperfusion injury and oxidative stress–mediated cell death. Increasing glutathione, but not Akt signaling, contributes to the protective effect of lipoic acid. Pretreating hNSCs with lipoic acid also increases the cell survival rate 1 month post-transplantation. Further investigation is warranted to develop improved techniques to maximize the survival of transplanted stem cells.
This research was supported by the National Institute of Neurological Disorders and Stroke (NS046025 to PW), the National Institutes of Health under Ruth L Kirschstein National Research Service Award (F30 NS060387 to JRT), the TIRR Foundation, the Gillson Longenbaugh Foundation, the John S Dunn Research Foundation, and the Cullen Foundation. The authors also thank Dr Richard Coggeshall for critical review.
© 2013 Gao et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.