Human amniotic fluid mesenchymal stem cells in combination with hyperbaric oxygen augment peripheral nerve regeneration.
OBJECTIVE
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.


CONCLUSIONS
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.
Pan
Hung-Chuan
HC
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Chin
Chun-Shih
CS
Yang
Dar-Yu
DY
Ho
Shu-Peng
SP
Chen
Chung-Jung
CJ
Hwang
Shiaw-Min
SM
Chang
Ming-Hong
MH
Cheng
Fu-Chou
FC
D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D006931:Hyperbaric Oxygenation; D008264:Macrophages / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D020426:Sciatic Neuropathy / Q000628:therapy*
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D009195:Peroxidase