Combined Bone Mesenchymal Stem Cell and Olfactory Ensheathing Cell Transplantation Promotes Neural Repair Associated With CNTF Expression in Traumatic Brain-Injured Rats.

This study examined the role of bone mesenchymal stem cell (BMSC) and olfactory ensheathing cell (OEC) cografting on neural function and underlying molecular mechanisms in acute stage of traumatic brain injury (TBI) rats. Eighty Sprague-Dawley (SD) female rats were randomly divided into five groups (n = 16 per category): sham operated group (Sham), weight-drop-induced TBI group (TBI), BMSC transplantation group (BMSC), OEC transplantation group (OEC), and cotransplantation group (CO). Eight rats were randomly selected from each group for behavioral and morphological assessment. Another category (n = 8 rats) was employed in the genetic expression detection. BMSCs were isolated from GFP mice and identified by CD44 antibody. OECs were isolated from the SD rats, identified by P75 antibody and labeled by Hoechst 33342. They were then transplanted into the surrounding tissue of the epicenter of TBI rats. The result of neurological severity scores revealed that BMSC or OEC transplantation alone and BMSC and OEC cografting significantly ameliorated the neurological deficits of TBI rats. Quantitative immunohistochemical analysis showed that graft-recipient animals possessed dramatically more neurons and regenerated axons and smaller amounts of astrocytes than controls 14 days posttransplantation (p < 0.05). However, the expressional level of ciliary neurotrophic factor significantly decreased in the cografting group as determined by RT-PCR (p < 0.05), and the Janus kinase/signal transducer and activator of transcription pathway was significantly activated at 7 days after cell transplantation (p < 0.05). This study is the first to report the role of cotransplantation of BMSCs and OECs in the therapy of TBI and explore its potential molecular mechanisms, therefore providing the important morphological and molecular biological evidence for the clinical application of BMSC and/or OEC transplantation in TBI.

Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism.

BACKGROUND: We sought to investigate the effects of co-grafting neural stem cells (NSCs) with olfactory ensheathing cells (OECs) on neurological behavior in rats subjected to traumatic brain injury (TBI) and explore underlying molecular mechanisms. METHODS: TBI was established by percussion device made through a weight drop (50 g) from a 30 cm height. Cultured NSCs and OECs isolated from rats were labeled by Hoechst 33342 (blue) and chloromethyl-benzamidodialkyl carbocyanine (CM-Dil) (red), respectively. Then, NSCs and/or OECs, separately or combined, were transplanted into the area surrounding the injury site. Fourteen days after transplantation, neurological severity score (NSS) were recorded. The brain tissue was harvested and processed for immunocytochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Significant neurological function improvement was observed in the three transplant groups, compared to the TBI group, and co-transplantation gave rise to the best improvement. Morphological evaluation showed that the number of neurons in cortex from combination implantation was more than for other groups (P <0.05); conversely, the number of apoptotic cells showed a significant decrease by TUNEL staining. Transplanted NSCs and OECs could survive and migrate in the brain, and the number of neurons differentiating from NSCs in the co-transplantation group was significantly greater than in the NSCs group. At the molecular level, the expressions of IL-6 and BAD in the co-graft group were found to be down regulated significantly, when compared to either the NSC or OEC alone groups. CONCLUSION: The present study demonstrates for the first time the optimal effects of co-grafting NSCs and OECs as a new strategy for the treatment of TBI via an anti-inflammation mechanism.

OECs transplantation results in neuropathic pain associated with BDNF regulating ERK activity in rats following cord hemisection.

BACKGROUND: The olfactory ensheathing cells (OECs) derived from olfactory bulb (OB) may improve motor function after transplantation in injured spinal cord. However, the effects of OEC transplantation on sensory function have not been reported yet. The purpose of this study is to investigate whether OEC transplantation could affect the sensory function and to analyze the underlying mechanism. RESULTS: OEC transplantation into the hemisected spinal cords can result in hyperalgesia, indicated by radiant and mechanical stimuli towards the plantar surface in rats. This could be associated with upregulation of Brain Derived Neurotrophic Factor (BDNF), indicated by RT-PCR. Immunofluorecent staining showed that BDNF was mainly located in the neurons of the laminas I and II of the dorsal horn. Moreover, a notable upregulation on the level of p-ERK (phosphorylation of extracellular signal-regulated kinase), the downstream molecule of BDNF, was detected by using Western Blot. These findings indicate that the increased BDNF level associated with the p-ERK was possibly involved in neuropathic pain in hemisected spinal cord subjected to OEC transplantation. CONCLUSIONS: The transplantation of OECs may induce the noticeable pain hypersensitivity in rats after hemisected spinal cord injury, and the possible mechanism may be associated with the phosphorylation of ERK and the activated BDNF overexpression.