New Strategy for Reconstruction of Denervated Muscles Using Motor Neuron Progenitors Derived from Mouse ES Cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20048
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Aichi Medical University (2017-2018); Nagoya University (2016)
• Principal Investigator: Shinkai Hiroki 愛知医科大学, 神経内科, 客員研究員 (50770898)
• Research Collaborator: Okada Yohei
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 末梢神経機能再建 / 運動神経前駆細胞 / 細胞移植 / 脱神経筋の神経再支配

Outline of Final Research Achievements

The aim of this study is to re-control the denervated muscle in case of
lower motor neuron dysfunction by the transplantation of ES cell-derived motor neuron progenitors (MNPCs) into the injured peripheral nerve.
After the transection of the sciatic nerve of rats / mice, MNPCs were implanted into the nerve stump. In case of xenotransplantation, immunosuppression by FK506 was also used. We performed histological evaluation of cell engraftments in transplanted area, functional analysis of the contraction of gastrocnemius muscle by electrical stimulation of nerve stump, and measurement of gastrocnemius muscle wet weight. Functional improvement of peripheral nerves were considered to be accomplished by MNPCs transplantation, though further analysis is required.

Free Research Field

手外科

Academic Significance and Societal Importance of the Research Achievements

異種移植での免疫抑制下における細胞移植によって末梢神経機能再建が得られた。免疫抑制は神経再生に重要で、免疫のコントロール次第で移植細胞の生着もしくは腫瘍化が生じるものと考える。組織学的に移植部分に移植細胞を認めずとも神経刺激による筋収縮を認めた。さらに移植のための免疫抑制のよりよい方法、腫瘍化をきたす未分化細胞の除去を行うこと、移植細胞の動態を調べることで、最終的にはヒト神経細胞のヒト末梢神経への移植により、ヒトの末梢神経障害による麻痺筋の機能再建をなすことができると考えられる。