Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration |
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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 |
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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.; |
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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. |
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Keywords: | Apoptosis Amniotic fluid mesenchymal stem cells Hyperbaric oxygen Sciatic nerve injury Inflammatory cytokines |
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