Neurological Surgery 脳神経外科39巻1号

2011年01月発行

総説

中枢神経疾患に対する細胞移植療法を用いた再生治療

著者： 金村米博¹²

所属機関： ¹国立病院機構大阪医療センター臨床研究センター再生医療研究室 ²国立病院機構大阪医療センター脳神経外科

ページ範囲：P.5 - P.23

Ⅰ．はじめに

　中枢神経疾患に対する再生治療法の研究開発は，現在，さまざまなアプローチを用いて全世界で精力的に研究が実施されている．研究対象となる疾病は，虚血性疾患や外傷性疾患など，脳神経外科医になじみの深い疾患に加え，神経変性疾患や先天性神経疾患など，従来は神経内科および小児科領域で主に加療されている疾病も加わり，多岐にわたる．研究の方向性としては，神経組織内に備わる幹細胞を代表とする内在性細胞を活用して疾病を治療するアプローチと，外部から何らかの細胞を移植・補充して治療を行うアプローチ（細胞移植療法：cell therapy）の2つに大別される．外科領域に近い治療法としては，後者の細胞移植療法が考えられ，現在までさまざまな細胞を応用した神経疾患の細胞移植療法が研究されてきた（Table 1）．

　細胞移植療法が神経症状改善をもたらすメカニズムとしては，移植細胞がホスト脳内に定着して，軸索再伸展による神経回路網の再構築や再髄鞘化を促すなどの直接的な神経再生作用（neuroregenerative effect）に加えて，細胞変性や細胞死を防ぐ神経保護作用（neuroprotective effect）が存在する．移植された細胞がこれらの作用のいずれを発揮するかは，細胞の種類，移植方法，移植時期により異なるが，何らかのメカニズムをもってして神経機能改善に貢献していると考えられる．歴史的には，胎児神経組織を代表とするさまざまな細胞，組織が基礎研究のみならず臨床研究においても移植に使用され，さらに嗅神経鞘細胞（グリア）（olfactory ensheathing cell/glia：OEC）^9,84)，臍帯血細胞（umbilical cord blood：UCB）⁶²⁾などの応用が報告されてきた（Table 1）．一方，昨今はin vitroで増殖させることが可能な神経幹細胞（neural stem cell：NSC）や間葉系幹細胞（mesenchymal stem cell：MSC）などの組織幹細胞，ES細胞やiPS細胞⁹⁴⁾などの多能性幹細胞，といった各種幹細胞の応用に注目が集まり，幹細胞あるいはそれに派生する分化細胞を用いた研究が精力的に実施され，続々と新しい臨床研究が開始あるいは準備されている（Table 2）．急速に拡大している本領域においては毎月のように多数の研究論文が報告されており，その全容を把握することは本領域の専門家でさえ困難である．個別領域においても，蓄積されている知見の量は膨大なものになりつつあり，限られた紙面でそのすべてを紹介することには限界がある．しかし，大きな進歩があるがゆえに，本領域の現状と将来性，特に脳神経外科領域の臨床現場における位置づけを見極める作業を継続的に行うことが，今後ますます重要になってくると考える．

　そこで本稿では，細胞移植療法を用いた治療法，とりわけ将来的に脳神経外科医が中心となって担うであろう「神経組織内移植」の有用性の検討がなされている研究の中から，既に臨床研究が開始されている，あるいはその開始が近い疾患を中心に，本領域の現状を概説する．なお，虚血性疾患への応用に関しては，既に本誌でも何度か概説されており，今回は割愛する．

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