Transplantation of activated olfactory ensheathing cells by curcumin strengthens regeneration and recovery of function after spinal cord injury in rats |
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| Affiliation: | 1. Department of Joint Surgery, Hong Hui Hospital, Xi''an Jiaotong University, Xi''an, China;2. Department of Geriatrics, Xijing Hospital, the Fourth Military Medical University, Xi''an, China;3. Department of Anesthesiology, the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang Shaanxi, China;4. Translational Medicine Center, Hong Hui Hospital, Xi''an Jiaotong University, Xi''an, China;5. Department of Spine Surgery, Hong Hui Hospital, Xi''an Jiaotong University, Xi''an, China;1. Seta Clinic Group, Tokyo, Japan;2. Department of Next-Generation Cell and Immune Therapy, Juntendo University School of Medicine, Tokyo, Japan;3. Kanazawa Advanced Medical Center, Kanazawa, Japan;4. Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan;1. University of Maryland School of Medicine, Baltimore, Maryland, USA;2. Biomedical Excellence for Safer Transfusion (BEST);3. Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA;4. Molecular and Cellular Therapeutics, University of Minnesota, Saint Paul, Minnesota, USA;5. Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA;6. Japanese Red Cross Society Blood Service Headquarters, Tokyo, Japan;7. Institut für Klinische Transfusionsmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany;8. NHS Blood and Transplant, The John Radcliffe Hospital, Oxford, UK;9. University of Utah, Salt Lake City, Utah, USA |
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| Abstract: | Background aimsThe pro-regeneration capabilities of olfactory ensheathing cells (OECs) remain controversial. However, little is known regarding whether the transplantation of activated OECs by curcumin (CCM) elicits neural regeneration and functional recovery after spinal cord injury (SCI) in rats, and the possible molecular mechanisms have never been investigated.MethodsPrimary OECs were treated with 1μM CCM for 1–3 days. Concomitantly, activated OECs were transplanted into the traumatic spinal cord of Sprague Dawley rats. One to 9 weeks after surgery, the assessment of behavior recovery was made using the Basso, Beattie and Bresnahan (BBB) locomotor scale; electrophysiology tests, such as somatosensory evoked potential (SEP) and motor evoked potential (MEP); and the cylinder test. Pathological study, including hematoxylin and eosin staining and immunofluorescence staining for neurofilaments (NFs), was conducted at 5 weeks post-surgery. In addition, activation profiles of OECs by CCM stimulus were assessed and levels of transglutaminase-2 (TG2) and phosphatidylserine receptor (PSR) in OECs stimulated by CCM were further determined.ResultsCCM remarkably enhanced OEC proliferation, improved cell viability and strengthened secretion of neurotrophins and anti-inflammatory factors. In addition, the levels of TG2 and PSR in CCM-treated OECs were significantly elevated. More importantly, beyond 1 week post-transplantation of CCM-treated OECs into lesioned spinal cord, BBB score and cylinder test score were significantly higher than that seen in the other three groups and a more postponed latent SEP and MEP period was noted. Furthermore, 5 weeks later, numerous, well-arranged NF-positive nerve fibers, lesions with less cavities and reduced levels of pro-inflammatory cytokines were found in activated OEC implantation groups. In addition, the number of NF-positive fibers was significantly improved and the number and area of both cavities and gliotic scars were remarkably decreased compared with the corresponding controls.ConclusionsTransplantation of OECs activated by CCM promotes neural regeneration and functional recovery following SCI, the underlying mechanisms of which are intimately associated with the elevated production of neurotrophic factors and anti-inflammatory factors in OECs stimulated by CCM as well as reduced pro-inflammatory cytokines from the post-contusion spinal cord. In addition, OECs activated by CCM were mediated through TG2 and PSR. |
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