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Impact of Dental Pulp Stem Cells Overexpressing Hepatocyte Growth Factor after Cerebral Ischemia/Reperfusion in Rats
Author(s) -
Kota Sowa,
Chikako Nito,
Masataka Nakajima,
Satoshi Suda,
Yasuhiro Nishiyama,
Yuki Sakamoto,
Yuko NitaharaKasahara,
Aki Nakamura-Takahashi,
Masayuki Ueda,
Kazumi Kimura,
Takashi Okada
Publication year - 2018
Publication title -
molecular therapy — methods and clinical development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 32
ISSN - 2329-0501
DOI - 10.1016/j.omtm.2018.07.009
Subject(s) - hepatocyte growth factor , hepatocyte , dental pulp stem cells , ischemia , stem cell , medicine , microbiology and biotechnology , chemistry , biology , biochemistry , in vitro , receptor
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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