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In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation. The gel graft containing the NSC and positively charged gold nanoparticles (pGNP) was implanted into spinal cord lesions in Sprague–Dawley rats (NSC‐pGNP gel group). Cellular differentiation of grafted NSCs into neurons (stained with β‐tubulin III [also called Tuj1]) was significantly increased in the NSC‐pGNP gel group (***p < 0.001) compared to those of two control groups (NSC and NSC gel groups) in the SCI conditions. The NSC‐pGNP gel group showed the lowest differentiation into astrocytes (stained with glial fibrillary acidic protein). Regeneration of damaged axons (stained with biotinylated dextran amines) within the lesion was two‐fold higher in the NSC‐pGNP gel group than that in the NSC gel group. The highest locomotor scores were also found in the NSC‐pGNP gel group. These outcomes suggest that neuron‐inducing pGNP gel graft embedding embryonic spinal cord‐derived NSCs can be a useful type of stem cell therapy after SCI. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)‐induced M2‐phenotype (M2) macrophages and their ability to promote anti‐neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model. Methods: To this end, compared to the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), we evaluated whether TUDCA effectively differentiates bone marrow–derived macrophages (BMDMs) into M2 macrophages. Results: The M2 expression markers in the TUDCA‐treated BMDM group were increased more than those in the GM‐CSF‐treated BMDM group. After the SCI and transplantation steps, pro‐inflammatory cytokine levels and the mitogen‐activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA‐induced M2 group more than they were in the GM‐CSF‐induced M1 group and in the TUDCA group. Moreover, the TUDCA‐induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM‐CSF‐induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)–labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA‐induced M2 group more than those in the GM‐CSF‐induced M1 group and the TUDCA group. Conclusions: This study demonstrates that the transplantation of TUDCA‐induced M2 macrophages promotes an anti‐neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA‐induced M2 macrophages represents a possible alternative cell therapy for SCI. [ABSTRACT FROM AUTHOR]

[Display omitted] • The synthesized aligned poly(lactic-co-glycolic acid) nanofibrous mat containing gold nanoparticles provides hydrophilic characteristics. • The nanofibrous mat conjugated with gold nanoparticles decreased the inflammatory responses. • The planted nanofibrous mat noticeably increased the cell survival and neuronal differentiation of transplanted neural stem cells. Transplanted cells rarely survive because of the inflammatory cytokines after spinal cord injury. To increase the survival, we synthesized a hydrophilic and aligned nanofibrous mat. We electrospun thiolate (SH)/aligned (A) poly(lactic-co-glycolic acid) (PLGA) nanofibrous mats. The PLGA-SH (A) nanofibrous mats were conjugated with gold nanoparticles (GNPs) to increase the hydrophilicity. The contact angle is decreased from 105.3° ± 5.2 (for randomly directional PLGA mats) to 28.1° ± 2.8 (for PLGA-GNP (A) mats). Green fluorescent protein (GFP)-expressing neural progenitor cells (NPCs) were dissociated from the embryonic spinal cords of Fisher 344 rats. We embedded the embryonic spinal-cord-derived NPCs in glycol chitosan (gC)-oxidized hyaluronate (oHA) hydrogels (=NPC graft). The NPC graft was transplanted into spinal-cord-injured Sprague-Dawley rats. Afterwards, the aligned PLGA-GNP nanofibrous mat was positioned onto the NPC-grafted region (=Injury + NPC graft + PLGA-GNP (A) nanofibrous mat (INP) group). We also added Injury (=I) and Injury + NPC graft (=IN) groups as control groups. The survival outcomes of transplanted NPCs were noticeably increased in the INP group compared to those in the IN group. We suggest a separate implanting therapy of NPCs and a hydrophilic PLGA-GNP (A) nanofibrous mat for spinal cord injuries. [ABSTRACT FROM AUTHOR]

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases. [ABSTRACT FROM AUTHOR]