Challenge to regeneration of the nigrostriatal dopaminergic neural projection by regulating cell adhesion molecules

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Izumi Yasuhiko 神戸薬科大学, 薬学部, 講師 (60456837)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: パーキンソン病 / ドパミン神経 / 線条体 / インテグリン

Outline of Final Research Achievements

Transplantation of stem cell-derived dopaminergic neurons is a promising therapeutic strategy for Parkinson's disease. Since we showed that the cell adhesion molecule integrin α5β1 is involved in striatal innervation by dopaminergic neurons, we investigated the effect of transplantation of integrin α5-overexpressing dopaminergic neurons into Parkinson's disease model mice. We succeeded in producing integrin α5 knock-in mouse embryonic stem cells, and differentiated them into dopaminergic neurons. They were transplanted to Parkinson's disease model mice, but the number of engrafts was very small, and it did not lead to improvement of the disease-like symptoms. In fact, it was found that the efficiency of differentiation of integrin α5 knock-in ES cells into dopaminergic nerves is low and that further investigations about differentiation induction methods and transplantation techniques are necessary to resolve it.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

幹細胞由来細胞の移植治療において、現在は、遺伝子変異の無い(無傷な)細胞移植が求められている。本研究のように、移植細胞の機能を高めるという考え方は、既存の概念からのパラダイムシフトを提示するものである。インテグリンα5β1の機能を高めることで黒質-線条体系ドパミン神経投射を再生することができれば、パーキンソン病に対して副作用が少なく治療効果が高い細胞移植療法に繋がる可能性がある。しかし、本研究の結果のように幹細胞は株ごとに異なる挙動を示すこともあるため、遺伝子操作した幹細胞株ごとでの分化条件の調整が必要であることが示された。