Therapeutic gene transfer enhances neuroprotective effects of dental pulp stem cells following focal cerebral ischemia ~ for clinical application ~

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Nippon Medical School
• Principal Investigator: Chikako Nito 日本医科大学, 医学部, 教授 (30409172)
• Co-Investigator(Kenkyū-buntansha): 須田 智 日本医科大学, 医学部, 准教授 (00366733)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 幹細胞治療 / 歯髄幹細胞 / AAVベクター / 脳保護効果 / 脳梗塞

Outline of Final Research Achievements

Administration of DPSCs (DPSC/HGF), in which hepatocyte growth factor (HGF) as a therapeutic gene was strongly expressed, to an acute ischemic stroke model showed a more significant infarct reduction than administration of DPSCs alone, and also showed significant improvement in the motor function of the animals. The mechanism of these effects was thought to be the suppression of neuronal cell death due to anti-inflammatory effects, the reduction of blood-brain barrier damage and the promotion of angiogenesis. Furthermore, tracing of the transplanted cells showed that no cell viability was observed in the ischaemic brain haemisphere after 14 days of reperfusion, suggesting that the transplanted DPSCs/HGF did not survive in the brain for a long time, and that the enhancement of HGF expression in the host was transient and caused few side effects such as immunosuppression.

Free Research Field

脳卒中

Academic Significance and Societal Importance of the Research Achievements

この研究成果は、遺伝子修飾を施した治療用細胞を損傷脳組織に導入し、適切な期間維持させる方法を開発する基盤となり、新規脳梗塞治療へとつながる可能性がある。