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Dec 17, 2006

ヒト腎臓再生:ラット体内で成功 世界初、幹細胞から

ひさしぶりに再生医療のトピックを拾ってみます。

ヒト腎臓再生:ラット体内で成功 世界初、幹細胞から

東京慈恵会医科大と自治医大の研究チームが、ラットの胎児の体内にヒトの骨髄液由来の幹細胞を埋め込み、ヒトの腎臓の一部(糸球体と尿細管)を作ることに世界で初めて成功した。その組織を別のラットの腹部に移植したところ、移植を受けたラットの血管が入り込み、通常のラットの腎臓の10分の1の大きさまで成長した。重い腎臓病に苦しむ患者が多い中、患者自身の細胞を使って人工的に腎臓を再生し、移植後も機能させる可能性につながる成果として注目される。(毎日新聞 2006年12月10日)

サイエンスとしては非常に面白いですし,将来性のある研究でしょう。ですが,記事にあるような医療応用としては,残念ながら期待どころかブレーキがかかりかねない研究といえます。

造血幹細胞の増幅や,ES細胞の未分化維持にマウスのフィーダー細胞を用いるだけでも,「異種移植」扱いとなって,培養した細胞は臨床応用できません。ましてやラット体内で育てた細胞となればなおさら慎重になる必要があります。

ヒトへ応用するには,やはり異種動物由来の細胞を使用しないことが最低限必要です。したがって,この技術が医療として陽の目を見るには,ヒトの体内で,組織を作り上げることができないといけません。

もとの論文に書いてあるように,彼らの研究の目的は,ドナー不足解消のために,自家移植,すなわち移植を望む本人の骨髄から採取した幹細胞を,腎臓組織に作り上げ,本人に戻すというものです。ですので,腎臓組織に必要な再構築は患者本人になります。そうでなければ代理母どころか,培養容器となるべき第一のレシピエントが必要となり,倫理的に重大な問題が発生するでしょう。

このアプローチでは(1)患者から骨髄採取→(2)腹膜下に移植→(3)出来上がった組織を腎臓へ移植,の3ステップが必要となります。

間葉系幹細胞は,その未分化性ゆえ癌化も心配されていますし,目的の組織以外の組織へ分化を制御させることもなかなか難しいですので,ステップ2での安全性を担保するのはなかなか大変といえます。したがって,この方法が腎臓移植に替わる医療となりうるのかといわれれば,残念ながら5年10年で可能とはやはり思えません。

とはいうものの,最初に書いたように,発生のメカニズム解析という部分では非常に面白いですし,発生研究のブレイクスルーになるかもしれません。

私の実感から言っても,組織の再構築は生体内でおこなう以上に効率よい場はありませんし,似たアイデアで再生できる他の組織もあるようです。大網に移植して,腎組織近くでは似た組織が再生するなら,なんらかの遠隔性に作用する液性因子の影響が考えられますので,そのあたりを切り口にして解析すれば,体外での3次元での組織構築という,再生医学者が現在夢にまでみる技術へ近づけるでしょう。移植したドナー細胞と,発生の場となるレシピエント細胞の間の細胞間相互作用も興味あるところです。実験結果からは,ヒトとラットの発生の間にはかなりの共通の因子も考えられそうです。

以下余談。医療技術として可能である,とかわざわざ喧伝しなくても,基礎として,いい研究なのは間違いないのですから,地道にすすめてほしいものです。神経再生の話なんかも5,6年前の総説を見ると,「2~3年で幹細胞を用いてヒトへ臨床応用可能」とか言っていました。現状では,まだ移植に足りるほど満足に分化誘導できません。そんな話はいくらでもあります。競争資金の獲得に,研究のPRが必要なのも理解していますが,あまり狼少年みたいにできないことを大げさに言っていては,再生医療全体がコケちゃうのではないでしょうか。
・・・え,もうコケてる!?つるかめつるかめ。

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