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Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury

View Article: PubMed Central - PubMed

ABSTRACT

Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.

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NSCs reduced neutrophil accumulation. (A) Representative images of spinal cord sections immunostained for 7/4 (anti-neutrophil antibody) at the injured area one week post-cell transplantation; (B) quantification of neutrophil infiltration at the injury site. Positive cells were counted in six sections from each mouse (five mice per group). Data are represented as the mean ± standard error. * p < 0.05. Scale bar: 100 μm.
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ijms-17-01380-f005: NSCs reduced neutrophil accumulation. (A) Representative images of spinal cord sections immunostained for 7/4 (anti-neutrophil antibody) at the injured area one week post-cell transplantation; (B) quantification of neutrophil infiltration at the injury site. Positive cells were counted in six sections from each mouse (five mice per group). Data are represented as the mean ± standard error. * p < 0.05. Scale bar: 100 μm.

Mentions: Furthermore, the number of neutrophils (control group: 256 ± 32 cells/mm2, NSC transplantation group: 105 ± 10 cells/mm2) was significantly decreased one week post-transplantation in the NSC group compared to the control group (p < 0.05) (Figure 5).


Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
NSCs reduced neutrophil accumulation. (A) Representative images of spinal cord sections immunostained for 7/4 (anti-neutrophil antibody) at the injured area one week post-cell transplantation; (B) quantification of neutrophil infiltration at the injury site. Positive cells were counted in six sections from each mouse (five mice per group). Data are represented as the mean ± standard error. * p < 0.05. Scale bar: 100 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037660&req=5

ijms-17-01380-f005: NSCs reduced neutrophil accumulation. (A) Representative images of spinal cord sections immunostained for 7/4 (anti-neutrophil antibody) at the injured area one week post-cell transplantation; (B) quantification of neutrophil infiltration at the injury site. Positive cells were counted in six sections from each mouse (five mice per group). Data are represented as the mean ± standard error. * p < 0.05. Scale bar: 100 μm.
Mentions: Furthermore, the number of neutrophils (control group: 256 ± 32 cells/mm2, NSC transplantation group: 105 ± 10 cells/mm2) was significantly decreased one week post-transplantation in the NSC group compared to the control group (p < 0.05) (Figure 5).

View Article: PubMed Central - PubMed

ABSTRACT

Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-&alpha; (TNF-&alpha;), interleukin-1&beta; (IL-1&beta;), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-&alpha;, IL-1&beta;, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-&alpha; and IL-1&beta; by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p &lt; 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p &lt; 0.05). Meanwhile, mRNA levels of TNF-&alpha;, IL-1&beta;, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p &lt; 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.

No MeSH data available.


Related in: MedlinePlus