PMID- 24042200 OWN - NLM STAT- MEDLINE DCOM- 20131115 LR - 20181202 IS - 1554-6578 (Electronic) IS - 0022-3069 (Linking) VI - 72 IP - 10 DP - 2013 Oct TI - Blockade of interleukin 6 signaling improves the survival rate of transplanted bone marrow stromal cells and increases locomotor function in mice with spinal cord injury. PG - 980-93 LID - 10.1097/NEN.0b013e3182a79de9 [doi] AB - Bone marrow stromal cells (BMSCs) have the potential to improve functional recovery in patients with spinal cord injury (SCI); however, they are limited by low survival rates after transplantation in the injured tissue. Our objective was to clarify the effects of a temporal blockade of interleukin 6 (IL-6)/IL-6 receptor (IL-6R) engagement using an anti-mouse IL-6R monoclonal antibody (MR16-1) on the survival rate of BMSCs after their transplantation in a mouse model of contusion SCI. MR16-1 cotreatment improved the survival rate of transplanted BMSCs, allowing some BMSCs to differentiate into neurons and astrocytes, and improved locomotor function recovery compared with BMSC transplantation or MR16-1 treatment alone. The death of transplanted BMSCs could be mainly related to apoptosis rather than necrosis. Transplantation of BMSC with cotreatment of MR16-1 was associated with a decrease of some proinflammatory cytokines, an increase of neurotrophic factors, decreased apoptosis rates of transplanted BMSCs, and enhanced expression of survival factors Akt and extracellular signal-regulated protein kinases 1/2. We conclude that MR16-1 treatment combined with BMSC transplants helped rescue neuronal cells and axons after contusion SCI better than BMSCs alone by modulating the inflammatory/immune responses and decreasing apoptosis. FAU - Tan, Ying AU - Tan Y AD - From the Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China (YT, SYL); Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan (YT, KU, HN, ARG, SW, TH, NT, HB); and Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (WEBJ). FAU - Uchida, Kenzo AU - Uchida K FAU - Nakajima, Hideaki AU - Nakajima H FAU - Guerrero, Alexander R AU - Guerrero AR FAU - Watanabe, Shuji AU - Watanabe S FAU - Hirai, Takayuki AU - Hirai T FAU - Takeura, Naoto AU - Takeura N FAU - Liu, Shao-Yu AU - Liu SY FAU - Johnson, William E B AU - Johnson WE FAU - Baba, Hisatoshi AU - Baba H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neuropathol Exp Neurol JT - Journal of neuropathology and experimental neurology JID - 2985192R RN - 0 (Interleukin-6) RN - 0 (Receptors, Interleukin-6) SB - IM MH - Animals MH - Cell Survival/*drug effects/physiology MH - Disease Models, Animal MH - Interleukin-6/*antagonists & inhibitors MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*drug effects MH - Mice MH - Motor Activity/*drug effects/physiology MH - Neurons/drug effects/physiology MH - Receptors, Interleukin-6/*antagonists & inhibitors MH - Recovery of Function/drug effects/physiology MH - Signal Transduction/drug effects MH - Spinal Cord Injuries/*drug therapy/physiopathology/surgery MH - Survival Rate EDAT- 2013/09/18 06:00 MHDA- 2013/11/16 06:00 CRDT- 2013/09/18 06:00 PHST- 2013/09/18 06:00 [entrez] PHST- 2013/09/18 06:00 [pubmed] PHST- 2013/11/16 06:00 [medline] AID - 10.1097/NEN.0b013e3182a79de9 [doi] PST - ppublish SO - J Neuropathol Exp Neurol. 2013 Oct;72(10):980-93. doi: 10.1097/NEN.0b013e3182a79de9.