Effect of Dental Pulp Stem Cells Overexpressing Therapeutic Gene in a Rat Stroke Model.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Nippon Medical School
• Principal Investigator: Nito Chikako 日本医科大学, 医学部, 准教授 (30409172)
• Co-Investigator(Kenkyū-buntansha): 須田 智 日本医科大学, 医学部, 講師 (00366733)
• Research Collaborator: Okada Takashi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 歯髄幹細胞 / 遺伝子治療 / 幹細胞移植 / 脳虚血

Outline of Final Research Achievements

We aimed increasing therapeutic effect combining DPSC and ex vivo human hepatocyte growth factor (HGF) gene transferring with AAV vector. Rats were subjected to transient MCAO, followed by intravenous administration of DPSC or HGF transferred DPSC (DPSC/HGF) or vehicle immediately after reperfusion. Infarct volume at 24 and 72 h after reperfusion were diminished in both DPSC and DPSC/HGF transplantation compared with vehicle. DPSC/HGF transplantation showed more reduction of infarct volume compared with DPSC. Motor function recovery was also observed at 24 and 72 h in both DPSC and DPSC/HGF transplantation. Furthermore, Both DPSC and DPSC/HGF group improved neuronal degeneration compared with vehicle. DPSC/HGF markedly decreased brain tissue TNF-α and IL-1β concentrations compared with vehicle and DPSC. These findings show that this combination therapy may enhance the neuroprotective effect of DPSC transplantation alone through the modulation of inflammation in cerebral ischemia.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトの病態に近づけた脳虚血に対し、細胞治療と遺伝子治療の併用療法を静脈投与という最も侵襲の少ない投与法により、その有効性と安全性を検討する点が独創的である。これらのことが証明できれば、本研究は脳梗塞という最もメジャーな中枢神経損傷疾患に対する新たな治療戦略の樹立へとつながり、高齢社会を迎え増加の一途をたどる虚血性脳血管障害の臨床に多大に貢献するものと考えている。