期刊
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
卷 10, 期 -, 页码 281-290出版社
CELL PRESS
DOI: 10.1016/j.omtm.2018.07.009
关键词
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资金
- JCR Pharmaceuticals Co., Ltd. (Hyogo, Japan)
- Ministry of Education, Culture, Sports, Science and Technology of Japan [26293328, 15K10317]
- Grants-in-Aid for Scientific Research [26293328, 15K10317] Funding Source: KAKEN
Hepatocyte growth factor (HGF) has neuroprotective effects against ischemia-induced injuries. Dental pulp stem cell (DPSC) transplantation attenuates tissue injury in the brain of rats with post-transient middle cerebral artery occlusion. We sought to determine whether DPSCs that overexpress HGF can enhance their therapeutic effects on brain damage post-ischemia/reperfusion injury. Treatment with DPSCs overexpressing HGF reduced infarct volumes compared to unmodified DPSC treatment at 3 and 7 days post-transient middle cerebral artery occlusion. The use of unmodified DPSCs and DPSCs overexpressing HGF was associated with improved motor function compared to that with administration of vehicle at 7 days post-transient middle cerebral artery occlusion. DPSCs overexpressing HGF significantly inhibited microglial activation and pro-inflammatory cytokine production along with suppression of neuronal degeneration. Post-reperfusion, DPSCs overexpressing HGF attenuated the decreases in tight junction proteins, maintained blood-brain barrier integrity, and increased microvessel density in peri-infarct areas. The administration of DPSCs overexpressing HGF during the acute phase of stroke increased their neuroprotective effects by modulating inflammation and blood-brain barrier permeability, thereby promoting improvements in post-ischemia/reperfusion brain injury.
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