Neurological Surgery 脳神経外科37巻12号

2009年12月発行

総説

脳虚血と神経再生

著者： 川原信隆¹

所属機関： ¹横浜市立大学大学院医学研究科脳神経外科学

ページ範囲：P.1165 - P.1177

Ⅰ．はじめに：神経再生へのさまざまなアプローチ

　近年の再生医学研究は急速な進展をみせており，失われた臓器の機能再建が現実の課題となりつつある．脳の機能再建も，困難な領域とされながらもさまざまな研究が展開されてきている（Fig. 1）．このような潮流の中で，古くから行われてきているのが，胎児脳組織を脳内に移植して機能再建を図る試みである⁶⁵⁾．しかしその一方で，免疫拒絶，感染，供給の限界，倫理上の問題などが取り上げられてきてもいる．未分化の胚性幹細胞の移植がこれらの一部の問題を解決するとして注目されているが，同種間移植では高率に腫瘍が発生し得ることが示されており³¹⁾，安全性の問題が残る．

　これらの問題を解決する方法として，成体自己組織幹細胞を用いた移植研究も行われてきている．骨髄^73,62)，皮膚^50,103)，脂肪組織⁹¹⁾などから神経分化能を有した体性幹細胞が分離されており，transdifferentiationと呼ばれている¹¹⁰⁾．しかし，in vivo移植実験では神経細胞への直接的分化能は極めて低いようで，細胞融合によるartifactではないかとの報告もなされている¹⁰¹⁾．また，より多分化能を獲得した細胞を誘導する方法としてiPS細胞（誘導多能性幹細胞：induced pluripotent stem cell）が最近話題となっている⁹⁹⁾．Oct3/4，Sox2，c-Myc，KLF4の4つの遺伝子を線維芽細胞に導入し，胚性幹細胞に近い多分化能を獲得した細胞を作成する方法であり，免疫，供給，倫理の問題などが解決可能となる画期的なものである．今後の移植治療において，飛躍的な発展が期待されている領域である¹¹³⁾．

　一方，成体脳内にも神経幹細胞が存在することが知られるようになり³⁴⁾，内在性神経幹細胞を用いた再生療法の可能性も模索されてきている．上記の移植治療と比較して，真の意味での脳の再生療法といえよう．しかし，哺乳類成体脳が損傷を受けたとき，内在性幹細胞から十分な神経修復がなされないことは事実であり，これらの幹細胞の存在部位，量の多寡，損傷応答や挙動など，神経再生を実現するためには，解決すべき問題点も多い．

　このように，脳虚血後に神経再生を試みる方法としてさまざまな手段が研究されており，そのいずれもが日進月歩で関連する領域の論文数も急速に増えてきている．そのすべてを虚血脳の再生という観点から解説することは，困難な課題であると同時に筆者の能力を超えるものでもある．したがって，本稿ではテーマを筆者らの共同研究グループが主に行ってきた内在性神経幹細胞を用いたアプローチに絞り，その現状と問題点について述べることとしたい．

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