Reconstruction of motor function with human iPS cells and optogenetics and application to diaphragmatic pacing

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21345
• Project/Area Number (Other): 18H06251 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Nagoya University
• Principal Investigator: SAEKI MASAOMI 名古屋大学, 医学部附属病院, 特任助教 (40822292)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 末梢神経損傷 / iPS細胞 / 末消神経再生 / オプトジェネティクス / チャネルロドプシン

Outline of Final Research Achievements

ChR2 (H134R) was introduced into motor neurons derived from human iPS cells using a lentiviral vector. Using a multi-electrode array, it was confirmed that blue light irradiation induced action potentials in motor neurons to which ChR2 (H134R) was introduced.
Human iPS cell-derived motoneurons introduced with ChR2 (H134R) were transplanted into a rat sciatic nerve transection model. Histological analysis 12 weeks after transplantation confirmed that engraftment of the transplanted cells and axons derived from the transplanted cells formed neuromuscular junctions in the muscles of rats, and muscle contraction and muscle action potentials were confirmed in approximately half of the animals by electrical stimulation. On the other hand, sufficient muscle action potentials were not observed with light stimulation.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

機能的電気刺激は実臨床において利用されている技術であり、当グループでの末梢神経損傷モデルにおける筋収縮も電気刺激により誘発された。しかし電気刺激は細胞特異的に刺激することが不可能であり、運動神経と感覚神経を含む横隔神経の刺激では、筋収縮のみでなく、不快感を誘発する。これに対し、光刺激は、移植前にあらかじめ細胞にChR2を導入しておくことで、低侵襲で、細胞特異的な刺激が可能である。末梢神経をターゲットとした運動機能再建において機能的電気刺激から機能的光刺激への移行は、臨床応用へ向けた重要な課題である。