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Stem Cell Reports. 2015 Aug 11;5(2):264-77. doi: 10.1016/j.stemcr.2015.06.004. Epub 2015 Jul 16.

Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury.

Author information

1
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
2
Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
3
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
4
Department of Advanced Medical Initiatives, JST-CREST, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
5
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
6
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: seokada@ortho.med.kyushu-u.ac.jp.

Abstract

Neural stem/progenitor cell (NSPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI). However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, but not after severe SCI. In severe SCI mice, there were few remaining host neurons within the range of NSPC engraftment; thus, we examined whether the co-distribution of transplant and host is a contributory factor for functional improvement. A cellular selective analysis using laser microdissection revealed that drug-induced host neuronal ablation considerably decreased the synaptogenic potential of the engrafted NSPCs. Furthermore, following host neuronal ablation, neuronal retrograde tracing showed less propriospinal relay connections bridging the lesion after NSPC transplantation. Our findings suggest that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery, providing significant insight for establishing therapeutic strategies for severe SCI.

PMID:
26190527
PMCID:
PMC4618657
DOI:
10.1016/j.stemcr.2015.06.004
[Indexed for MEDLINE]
Free PMC Article

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