title: 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.
abstract: 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.
authors.affiliation: 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).
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.forename: Kenzo
authors.initials: K
authors.lastname: Uchida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Guerrero
authors.forename: Shuji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hirai
authors.forename: Naoto
authors.initials: N
authors.lastname: Takeura
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Liu
authors.forename: William E B
authors.initials: WE
authors.lastname: Johnson
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Baba
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D015996:Survival Rate; D000093242:Interleukin-6 Inhibitors
chemical_list: D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors