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

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.

Strategies for CNS repair following TBI

“…Additionally, co-grafting of stem cells with another cell type has also been performed. Transplantation of NSC with olfactory ensheathing cells has been shown to result in a 3.4 fold increase in cell survival compared to NSC alone (Liu et al, 2014a). Cografting BM-MSC with Schwann cells has been reported to have effects separate from just changes in survival.…”

Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization

“…7 Stem cell transplantation is a promising candidate to treat SCI. [8][9][10][11][12] Recent work showed that stem cells, such as mesenchymal stem cells (MSCs), [13][14][15] neural stem/progenitor cells (NS/ PCs), 16,17 and embryonic stem cells (ESCs), [18][19][20] have immunoregulatory capacity and anti-inflammatory effects and could enhance functional improvement through inducing macrophages M1/M2 phenotype transformation post SCI. This review will discuss 1) the general feature of macrophages in response to SCI, 2) the phenotype and function of macrophages in SCI, and 3) the effects of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.…”

Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat

“…showing optimal effects of co-grafting NSCs with OECs in terms of promoting NSC survival and neuronal restoration after experimental traumatic brain injury and Parkinson's disease [29,30] .…”