Prior Treatment with Anti‐High Mobility Group Box‐1 Antibody Boosts Human Neural Stem Cell Transplantation‐Mediated Functional Recovery After Spinal Cord Injury. (8th March 2018)

• Record Type: Journal Article
• Authors: Uezono, Naohiro; Zhu, Yicheng; Fujimoto, Yusuke; Yasui, Tetsuro; Matsuda, Taito; Nakajo, Masahide; Abematsu, Masahiko; Setoguchi, Takao; Mori, Shuji; Takahashi, Hideo K.; Komiya, Setsuro; Nishibori, Masahiro; Nakashima, Kinichi
• Is Part Of: Stem cells. Volume 36:Number 5(2018)
• Page Start: 737
• Page End: 750
• Publication Date: 2018-03-08
• Subjects: Spinal cord injury -- High mobility group box‐1 -- Neural stem cell -- Transplantation -- Combinatorial treatment; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2802
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Together with residual host neurons, transplanted neural stem cell (NSC)‐derived neurons play a critical role in reconstructing disrupted neural circuits after spinal cord injury (SCI). Since a large number of tracts are disrupted and the majority of host neurons die around the lesion site as the damage spreads, minimizing this spreading and preserving the lesion site are important for attaining further improvements in reconstruction. High mobility group box‐1 (HMGB1) is a damage‐associated molecular pattern protein that triggers sterile inflammation after tissue injury. In the ischemic and injured brain, neutralization of HMGB1 with a specific antibody reportedly stabilizes the blood‐brain barrier, suppresses inflammatory cytokine expression, and improves functional recovery. Using a SCI model mouse, we here developed a combinatorial treatment for SCI: administering anti‐HMGB1 antibody prior to transplantation of NSCs derived from human induced pluripotent stem cells (hiPSC‐NSCs) yielded a dramatic improvement in locomotion recovery after SCI. Even anti‐HMGB1 antibody treatment alone alleviated blood‐spinal cord barrier disruption and edema formation, and increased the number of neurites from spared axons and the survival of host neurons, resulting in functional recovery. However, this recovery was greatly enhanced by the subsequent hiPSC‐NSC transplantation, reaching an extent that has never before been reported. We also found that this improved recovery was directly associated with connections established between surviving host neurons and transplant‐derived neurons. Taken together, our results highlight combinatorial treatment with anti‐HMGB1 antibody and hiPSC‐NSC transplantation as a promising novel therapy for SCI. Stem Cells 2018;36:737–750 Abstract : Anti‐high mobility group box‐1 monoclonal antibody treatment suppresses damage spread, increases sprouting neurites from spared axons, and enhances host neuronal survival after spinal cord injury, without affecting survival of transplanted cells. The increase in the number of sprouting neurites from spared axons and surviving host neurons enhances the likelihood that transplant‐derived neurons can make connections, resulting in improved functional recovery after spinal cord injury.