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

Su-Juan Liu,Xue Zhou,Na Lin,Long-Yun Lv,Ting-Yong Wang,Yu Zou,Qing-Jie Xia,Ting-Hua Wang,John W Mcdonald,Visar Belegu

doi:10.1186/1742-2094-11-66

Abstract

BackgroundWe 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.MethodsTBI 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).ResultsSignificant 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.ConclusionThe 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.

Highlights

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
The cells stained with nestin were confirmed as NSCs (Figure 1B)
NSCs exhibited the capacity to differentiate into neurons, astrocytes, and oligodendrocytes

Summary

Introduction

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. Traumatic brain injury (TBI) occurs as a result of direct mechanical insult to the brain, and induces degeneration and death in the central nervous system (CNS) [1,2]. 77.3% had good recovery, there was still a 10.8% mortality; 2.6% remained in a persistent vegetative state, 2.2% had severe disability, and 7.2% had moderate disability [4]. Much of this unfavorable outcome was due to secondary brain damage that occurred in the hours, days, and weeks after the primary insult [5]. Few interventions have been shown to be efficacious for the treatment of TBI in clinical trials [6], and it is necessary to develop new therapeutic interventions for the clinical treatment of TBI

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