title: Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury.
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.
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. czj.0606@stu.xjtu.edu.cn.
authors: Zhijian
authors: Z
authors: Cheng
authors: Intensive Care Unit, The First People's Hospital of Xianyang City, Xianyang 710021, China. zhuwen841008@163.com.
authors: Wen
authors: W
authors: Zhu
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. caokai@foxmail.com.
authors: Kai
authors: K
authors: Cao
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. wfhnsx@163.com.
authors: Fei
authors: F
authors: Wu
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. jin_lee1218@163.com.
authors: Jin
authors: J
authors: Li
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. wgy1509@126.com.
authors: Guoyu
authors: G
authors: Wang
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. lhp-3993@163.com.
authors: Haopen
authors: H
authors: Li
authors: Neurosurgery Department, The Second Affiliated Hospital of Hunan Normal University, Changsha 410003, China. lumingcs163@163.com.
authors: Ming
authors: M
authors: Lu
authors: Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, FL 32306, USA. yren055@gmail.com.
authors: Yi
authors: Y
authors: Ren
authors: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. xijing_h@vip.tom.com.
authors: Xijing
authors: X
authors: He
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D013119:Spinal Cord Injuries / Q000276:immunology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12
keywords: inflammatory cytokine; macrophage; neural stem cells; spinal cord injury