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

Ying Tan, Kenzo Uchida*, Hideaki Nakajima, Alexander R. Guerrero, Shuji Watanabe, Takayuki Hirai, Naoto Takeura, Shao-Yu Liu, William E.B. Johnson, Hisatoshi Baba

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)980-993
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords

  • apoptosis
  • bone marrow stromal cells
  • cell survival
  • inflammation
  • interleukin 6
  • spinal cord injury
  • transplantation

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