PMID- 27563878 OWN - NLM STAT- MEDLINE DCOM- 20170501 LR - 20220330 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 9 DP - 2016 Aug 23 TI - Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury. LID - 10.3390/ijms17091380 [doi] LID - 1380 AB - 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-1beta (IL-1beta), 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-1beta, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-alpha and IL-1beta 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-alpha, IL-1beta, 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. FAU - Cheng, Zhijian AU - Cheng Z AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. czj.0606@stu.xjtu.edu.cn. FAU - Zhu, Wen AU - Zhu W AD - Intensive Care Unit, The First People's Hospital of Xianyang City, Xianyang 710021, China. zhuwen841008@163.com. FAU - Cao, Kai AU - Cao K AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. caokai@foxmail.com. FAU - Wu, Fei AU - Wu F AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. wfhnsx@163.com. FAU - Li, Jin AU - Li J AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. jin_lee1218@163.com. FAU - Wang, Guoyu AU - Wang G AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. wgy1509@126.com. FAU - Li, Haopen AU - Li H AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. lhp-3993@163.com. FAU - Lu, Ming AU - Lu M AD - Neurosurgery Department, The Second Affiliated Hospital of Hunan Normal University, Changsha 410003, China. lumingcs163@163.com. FAU - Ren, Yi AU - Ren Y AD - Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, FL 32306, USA. yren055@gmail.com. FAU - He, Xijing AU - He X AD - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. xijing_h@vip.tom.com. LA - eng PT - Journal Article DEP - 20160823 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Cells, Cultured MH - Female MH - Immunohistochemistry MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Macrophages/cytology/physiology MH - Mice MH - Mice, Inbred C57BL MH - Neural Stem Cells/cytology/*physiology MH - Neutrophils/cytology/physiology MH - Spinal Cord Injuries/immunology/*therapy MH - Stem Cell Transplantation/*methods MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC5037660 OTO - NOTNLM OT - inflammatory cytokine OT - macrophage OT - neural stem cells OT - spinal cord injury COIS- The authors declare no conflict of interest. EDAT- 2016/08/27 06:00 MHDA- 2017/05/02 06:00 PMCR- 2016/09/01 CRDT- 2016/08/27 06:00 PHST- 2016/06/20 00:00 [received] PHST- 2016/08/08 00:00 [revised] PHST- 2016/08/11 00:00 [accepted] PHST- 2016/08/27 06:00 [entrez] PHST- 2016/08/27 06:00 [pubmed] PHST- 2017/05/02 06:00 [medline] PHST- 2016/09/01 00:00 [pmc-release] AID - ijms17091380 [pii] AID - ijms-17-01380 [pii] AID - 10.3390/ijms17091380 [doi] PST - epublish SO - Int J Mol Sci. 2016 Aug 23;17(9):1380. doi: 10.3390/ijms17091380.