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Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration
Authors:Hung-Chuan Pan  Chun-Shih Chin  Dar-Yu Yang  Shu-Peng Ho  Chung-Jung Chen  Shiaw-Min Hwang  Ming-Hong Chang  Fu-Chou Cheng
Institution:(1) Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan;(2) Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan;(3) Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan;(4) Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan;(5) Department of Neurosurgery, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan;(6) Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan;(7) Department of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan;(8) Stem Cell Center, Department of Medical Research, Taichung Veterans General Hospital, No. 160, Sec. 3, Taichung-Kang Road, Taichung, 407, Taiwan, R.O.C.;
Abstract:Purpose Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Methods Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Results Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. Conclusion AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.
Keywords:Apoptosis  Amniotic fluid mesenchymal stem cells  Hyperbaric oxygen  Sciatic nerve injury  Inflammatory cytokines
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