字幕表 動画を再生する
As humans, it's in our nature
翻訳: Reiko Bovee 校正: Eriko T
to want to improve our health and minimize our suffering.
誰もが 健康を改善したり
Whatever life throws at us,
肉体的苦しみを最小限に留め
whether it's cancer, diabetes, heart disease,
我が身に起る事が
or even broken bones, we want to try and get better.
癌 糖尿病 心臓病または骨折と
Now I'm head of a biomaterials lab,
それが何であろうと 良くなりたいと思うものです
and I'm really fascinated by the way that humans
私は生体材料研究所の所長ですが
have used materials in really creative ways
過去 様々な材料が 独創的な方法で人体に
in the body over time.
使われてきたということに
Take, for example, this beautiful blue nacre shell.
とても感心させられます
This was actually used by the Mayans
例えば この貝の青い真珠層をご覧下さい
as an artificial tooth replacement.
これはマヤ族が歯のインプラントに
We're not quite sure why they did it.
実際 使っていました
It's hard. It's durable.
その理由はよく分かりませんが
But it also had other very nice properties.
硬く長持ちし
In fact, when they put it into the jawbone,
他にもとても良い特質があります
it could integrate into the jaw,
顎に入れると
and we know now with very sophisticated
顎骨と融合するのです
imaging technologies
高度画像技術で
that part of that integration comes from the fact
分かっている
that this material is designed
融合の理由は この材料の
in a very specific way, has a beautiful chemistry,
用途によく合ったデザイン
has a beautiful architecture.
そして素晴らしい化学的性質と
And I think in many ways we can sort of think
構造にありました
of the use of the blue nacre shell and the Mayans
あらゆる意味で
as the first real application
マヤ族の青い真珠層を持つ貝の使い道は
of the bluetooth technology.
まさしく最初の
(Laughter)
ブルートゥース技術だ なんて思ったりします
But if we move on and think throughout history
(笑)
how people have used different materials in the body,
先に進んで 歴史を通して
very often it's been physicians
人類が体に様々な種類の材料を 使ってきたことを考えてみると
that have been quite creative.
創意工夫をしてきたのは 医師の場合が多く
They've taken things off the shelf.
彼らが様々な発明をしてきました
One of my favorite examples
その中でも 私のお気に入りは
is that of Sir Harold Ridley,
サー・ハロルド・リドリーのものです
who was a famous ophthalmologist,
彼は有名な眼科医で—
or at least became a famous ophthalmologist.
少なくとも そうなったのですが—
And during World War II, what he would see
第2次世界大戦中 彼は
would be pilots coming back from their missions,
戦線から戻って来たパイロットを見て
and he noticed that within their eyes
彼らの目の中に
they had shards of small bits of material
小さな異物のかけらが 入っているのに気がつきました
lodged within the eye,
興味深いことに
but the very interesting thing about it
その物質は炎症反応を
was that material, actually, wasn't causing
全く引き起こしていなかったのでした
any inflammatory response.
調べて分かったことは
So he looked into this, and he figured out
その物質は 小さなプラスチックのかけらで
that actually that material was little shards of plastic
スピットファイア戦闘機の天蓋から 来る物でした
that were coming from the canopy of the Spitfires.
それで彼はこの物質を
And this led him to propose that material
新しい眼内レンズの素材 として提唱したのです
as a new material for intraocular lenses.
PMMAと呼ばれるもので
It's called PMMA, and it's now used
毎年 何百万人の人の目に
in millions of people every year
白内障を防ぐ為に使われています
and helps in preventing cataracts.
この例は
And that example, I think, is a really nice one,
昔は機械的機能をさせる為に
because it helps remind us that in the early days,
よく生体不活性材料が 選ばれ
people often chose materials
使われていた ということを 示しています
because they were bioinert.
生体不活性材料を体に入れても
Their very purpose was to perform a mechanical function.
拒絶反応はありません
You'd put them in the body
しかし ここで私が述べたい事は
and you wouldn't get an adverse response.
再生医療は
And what I want to show you is that
生体不活性材料から
in regenerative medicine,
全く離れたということです
we've really shifted away from that idea
我々が積極的に探している材料は
of taking a bioinert material.
生体と作用する 生体活性材料で
We're actually actively looking for materials
生体内に入れられると
that will be bioactive, that will interact with the body,
そこで機能し
and that furthermore we can put in the body,
時が経つにつれ 生体内に吸収されるものです
they'll have their function,
このチャートをご覧下さい
and then they'll dissolve away over time.
これが示しているのは
If we look at this schematic,
細胞組織工学の 典型的アプローチです
this is showing you what we think of
普通患者から細胞を取り
as the typical tissue-engineering approach.
それを材料に入れ
We have cells there, typically from the patient.
非常に複雑なものに することもでき—
We can put those onto a material,
実験室で増殖するか
and we can make that material very complex if we want to,
患者の体に直接 戻すか どちらでもできます
and we can then grow that up in the lab
これが世界中で そして
or we can put it straight back into the patient.
我々の実験室でも 行われている方法です
And this is an approach that's used all over the world,
幹細胞について 本当に大切なことの1つは
including in our lab.
幹細胞は あらゆる組織に分化でき
But one of the things that's really important
又 そうなる傾向にあるので
when we're thinking about stem cells
幹細胞を入れる環境に
is that obviously stem cells can be many different things,
我々が必要な情報を 確実に組み込むと
and they want to be many different things,
目的の特定の組織に なるという事です
and so we want to make sure that the environment
世界中の実験室で 再生が試みられている組織のタイプは
we put them into has enough information
殆ど考え得る全ての組織 と言っていい程です
so that they can become the right sort
そんな組織の構造は
of specialist tissue.
かなり多様で
And if we think about the different types of tissues
患者の他の 隠れた病気とか健康問題が
that people are looking at regenerating
組織の再生法や
all over the world, in all the different labs in the world,
材料の使用法や
there's pretty much every tissue you can think of.
生化学的性質、 機能
And actually, the structure of those tissues
その他多くの特質に影響し それにより 我々の対処法も大きく変わってきます
is quite different, and it's going to really depend
組織は其々 異なる再生能力があります
on whether your patient has any underlying disease,
ここで思い出すのが 可哀想なプロメテウス
other conditions, in terms of how
危なっかしい決断をした彼は
you're going to regenerate your tissue,
ギリシャの神々に罰せられ
and you're going to need to think about the materials
岩に縛り付けられ 鷲が毎日
you're going to use really carefully,
彼の肝臓をついばみに来ます
their biochemistry, their mechanics,
彼の肝臓は毎日再生し
and many other properties as well.
そうやって来る日も来る日も
Our tissues all have very different abilities to regenerate,
永遠に神々に罰せられるのです
and here we see poor Prometheus,
肝臓はこのように 再生されることになるでしょうが
who made a rather tricky career choice
他の組織
and was punished by the Greek gods.
例えば軟骨は
He was tied to a rock, and an eagle would come
どんな些細な欠損でも
every day to eat his liver.
再生するのは とても難しいのです
But of course his liver would regenerate every day,
この様に組織により 違いが非常に大きく
and so day after day he was punished
骨の再生能力はその中間です
for eternity by the gods.
骨は我々の実験室で よく扱われる組織の1つで
And liver will regenerate in this very nice way,
自己修復能力は 実は かなり高いのです
but actually if we think of other tissues,
そうでなければ困ります たぶん我々はみな
like cartilage, for example,
骨折を経験しているでしょうし
even the simplest nick and you're going to find it
骨折治療の1つの方法は
really difficult to regenerate your cartilage.
「腸骨採取」と呼ばれる手法で
So it's going to be very different from tissue to tissue.
外科医が
Now, bone is somewhere in between,
腸骨から骨を採取し
and this is one of the tissues that we work on a lot in our lab.
ここにありますが—
And bone is actually quite good at repairing.
体の他の部分にそれを移植します
It has to be. We've probably all had fractures
これは本当にうまく行くのです
at some point or other.
本人の骨なので
And one of the ways that you can think
うまく血管新生化し
about repairing your fracture
血液の流れが とても良くなるのですが
is this procedure here, called an iliac crest harvest.
問題は採骨できる量に 限界があるという事です
And what the surgeon might do
その上 手術後 採骨した場所が
is take some bone from your iliac crest,
2年経っても
which is just here,
非常に痛む可能性があるのです
and then transplant that somewhere else in the body.
それで我々が考えた事は
And it actually works really well,
勿論 骨修復の需要は 非常に大きいのですが—
because it's your own bone,
腸骨タイプのアプローチでは
and it's well vascularized,
限界があまりにあるので
which means it's got a really good blood supply.
必要に応じ 生体内で
But the problem is, there's only so much you can take,
骨を再生し 移植したらどうだろう
and also when you do that operation,
それにより腸骨採取後のような
your patients might actually have significant pain
極度の痛みが伴わない移植が
in that defect site even two years after the operation.
出来るのではないだろうか? ということです
So what we were thinking is,
その我々のやり方は
there's a tremendous need for bone repair, of course,
典型的な細胞組織工学の アプローチに戻ったのですが
but this iliac crest-type approach
かなり違った観点を取りました
really has a lot of limitations to it,
随分 簡素化して
and could we perhaps recreate
かなりステップを省きました
the generation of bone within the body
患者からの 細胞採取の必要性
on demand and then be able to transplant it
あらゆる高価な 化学薬品の必要性
without these very, very painful aftereffects
そして研究室で担体を
that you would have with the iliac crest harvest?
培養する必要性を なくしました
And so this is what we did, and the way we did it
我々が本当に 焦点を置いているのは
was by coming back to this typical tissue-engineering approach
材料系と それを簡素化する事ですが
but actually thinking about it rather differently.
よく考えられた方法で使用したので
And we simplified it a lot,
このアプローチによって
so we got rid of a lot of these steps.
膨大な量の骨を 再生できたのです
We got rid of the need to harvest cells from the patient,
それで我々は生体を
we got rid of the need to put in really fancy chemistries,
骨を大量に作る為の
and we got rid of the need
媒体として使いました
to culture these scaffolds in the lab.
そのアプローチを
And what we really focused on
「生体バイオリアクター」と呼び このやり方で
was our material system and making it quite simple,
とてつもない量の骨を 再生できるのです
but because we used it in a really clever way,
分かり易く説明すると
we were able to generate enormous amounts of bone
こうです
using this approach.
生体には幹細胞の層が
So we were using the body
長骨の外側にあり
as really the catalyst to help us
「骨膜」とよばれ
to make lots of new bone.
普段とても
And it's an approach that we call
しっかりと その下の骨に密着していて
the in vivo bioreactor, and we were able to make
幹細胞を含んでいます
enormous amounts of bone using this approach.
この幹細胞は
And I'll talk you through this.
胎芽の成長にとても重要で
So what we do is,
骨折すると
in humans, we all have a layer of stem cells
骨を修復しようと活性化します
on the outside of our long bones.
我々はその骨膜に目をつけ
That layer is called the periosteum.
その下に液体を 注入する方法を開発しました
And that layer is actually normally
その液体は注入後30秒内で
very, very tightly bound to the underlying bone,
固形のゲルになり
and it's got stem cells in it.
骨から骨膜を持ち上げる事ができ
Those stem cells are really important
人工の空洞が
in the embryo when it develops,
骨と幹細胞豊かな骨膜の間にできます
and they also sort of wake up if you have a fracture
微小な切り口から入るので
to help you with repairing the bone.
生体の他の細胞は入れません
So we take that periosteum layer
人工的に作られた空洞 バイオリアクター・スペースが
and we developed a way to inject underneath it
幹細胞の増殖に繋がり
a liquid that then, within 30 seconds,
多くの新しい組織を作り
would turn into quite a rigid gel
時が経つと組織を採取し
and can actually lift the periosteum away from the bone.
人体の他の場所に移植できます
So it creates, in essence, an artificial cavity
これがそのプロセスで見られる
that is right next to both the bone
組織構造のスライドです
but also this really rich layer of stem cells.
我々が見ているのは
And we go in through a pinhole incision
非常に大量の骨です
so that no other cells from the body can get in,
この写真では足の中の中央部—
and what happens is that that artificial in vivo bioreactor cavity
骨髄が右端に見え
can then lead to the proliferation of these stem cells,
次に本来の骨があり
and they can form lots of new tissue,
その骨が終わった所の
and then over time, you can harvest that tissue
丁度左に新生骨が
and use it elsewhere in the body.
バイオリアクター・スペース内で 再生しています
This is a histology slide
もっと大きくもできます
of what we see when we do that,
本来の骨と新生骨との
and essentially what we see
境界部分は
is very large amounts of bone.
ほんの少しだけですが弱い所で
So in this picture, you can see the middle of the leg,
ここが外科医の出番です
so the bone marrow,
新生骨を採取し
then you can see the original bone,
骨膜が再生します
and you can see where that original bone finishes,
初めっから手術など
and just to the left of that is the new bone
しなかったような状態の
that's grown within that bioreactor cavity,
足が戻ってきます
and you can actually make it even larger.
それで術後の痛みは
And that demarcation that you can see
腸骨採集後と比べれば とても軽いのです
between the original bone and the new bone
骨再生量は
acts as a very slight point of weakness,
ゲルの注入量次第なので
so actually now the surgeon can come along,
必要に応じて調節できます
can harvest away that new bone,
我々が これを公表した時
and the periosteum can grow back,
メディアの注目を浴びました
so you're left with the leg
新しい骨再生の
in the same sort of state
実にいい方法だからです
as if you hadn't operated on it in the first place.
これを使いたいと言う
So it's very, very low in terms of after-pain
様々な人々から問い合わせが来ました
compared to an iliac crest harvest.
実のところ
And you can grow different amounts of bone
全くおかしなものもありました
depending on how much gel you put in there,
思ってもなかったような
so it really is an on demand sort of procedure.
とっても面白いもの
Now, at the time that we did this,
と言ったらいいでしょう
this received a lot of attention in the press,
その1つは 米国のフットボール選手からで
because it was a really nice way
自分たちの頭蓋骨の厚みを 2倍にしたいというものでした
of generating new bone,
こんな問い合わせは 本当にあるのです
and we got many, many contacts
フランスで育った
from different people that were interested in using this.
イギリス人の私は
And I'm just going to tell you,
ちょっと辛口な傾向があり
sometimes those contacts are very strange,
彼らにこう説明しました
slightly unexpected,
「あなた達の様な特殊ケースでは
and the very most interesting,
たぶんその中にはあまり
let me put it that way, contact that I had,
守るものなんて ないんじゃないの」って
was actually from a team of American footballers
(笑)
that all wanted to have double-thickness skulls
(拍手)
made on their head.
これが我々のアプローチでした
And so you do get these kinds of contacts,
単純な材料ですが
and of course, being British
入念に計画しました
and also growing up in France,
生体や胎芽の幹細胞が
I tend to be very blunt,
成長すると
and so I had to explain to them very nicely
ある異なる組織の 軟骨になるのが分かっているので
that in their particular case,
少し化学的性質の違うゲルを開発し
there probably wasn't that much in there
それを注入し軟骨を100%
to protect in the first place.
再生できました
(Laughter)
これはあらかじめ計画されると とてもうまく行くやり方で
(Applause)
前もって計画しなければ ならないものです
So this was our approach,
他の手術では
and it was simple materials,
他の担体を基礎とした アプローチが確かに必要です
but we thought about it carefully.
他の担体を開発する時は
And actually we know that those cells
様々な分野からの 専門家チームが必要です
in the body, in the embryo, as they develop
我々のチームには化学者
can form a different kind of tissue, cartilage,
細胞生物学者 外科医 そして物理学者さえもが加わり
and so we developed a gel that was slightly different
皆で一体となり
in nature and slightly different chemistry,
材料の開発に懸命に 取り組んでいます
put it in there, and we were able to get
特定の細胞機能をさせるよう また実用化に向け複雑にならないよう
100 percent cartilage instead.
材料には 十分な情報を
And this approach works really well, I think,
備えて欲しいのです
for pre-planned procedures,
我々の仕事の1つは
but it's something you do have to pre-plan.
生体組織構造の理解を 深める事です
So for other kinds of operations,
骨について考えると
there's definitely a need for other
私が関心を持つ組織ですが—
scaffold-based approaches.
ズームインしてみると
And when you think about designing
皆さんが骨組織の事は よく知らなくても
those other scaffolds, actually,
本当に素晴らしく 組織化されていると分かります
you need a really multi-disciplinary team.
そこには血管が張り巡っています
And so our team has chemists,
更にズームインすると
it has cell biologists, surgeons, physicists even,
ナノスケール繊維の
and those people all come together
3D基質が細胞を囲み
and we think really hard about designing the materials.
細胞に多くの情報を与えています
But we want to make them have enough information
更にズームインすると
that we can get the cells to do what we want,
骨の場合 細胞周辺の基質は美しく
but not be so complex as to make it difficult
ナノスケールで纏まり
to get to clinic.
混成された
And so one of the things we think about a lot
有機・無機質のハイブリッドです
is really trying to understand
ここで全く新しい分野
the structure of the tissues in the body.
ハイブリッド的な構造を持った 材料の開発分野に移り
And so if we think of bone,
その例を2つだけお見せします
obviously my own favorite tissue,
ハイブリッド的構造を持った
we zoom in, we can see,
調整可能な材料を作りました
even if you don't know anything about bone structure,
ここにブヨブヨした物が見えますが
it's beautifully organized, really beautifully organized.
これもハイブリッド的材料で
We've lots of blood vessels in there.
驚く程強く
And if we zoom in again, we see that the cells
壊れ易くありません
are actually surrounded by a 3D matrix
無機質の材料は通常とても脆く
of nano-scale fibers, and they give a lot
このような丈夫さや強さはありません
of information to the cells.
もう1つだけちょっと 触れておきたい事は
And if we zoom in again,
我々が作る担体の多くは
actually in the case of bone, the matrix
そこに血管が通り 育つように多孔質です
around the cells is beautifully organized
穴のサイズは
at the nano scale, and it's a hybrid material
細胞より大きく
that's part organic, part inorganic.
3Dではありますが
And that's led to a whole field, really,
細胞には少しカーブした表面のように 見えるかもしれませんね
that has looked at developing materials
少々不自然です
that have this hybrid kind of structure.
ですから 考えないといけないのは
And so I'm showing here just two examples
担体を少し違う次元で
where we've made some materials that have that sort of structure,
3Dで細胞を包み
and you can really tailor it.
もう少し情報を 細胞に与えるように作る事です
You can see here a very squishy one
これらの領域では 色々な研究がなされています
and now a material that's also this hybrid sort of material
最後に少しだけ
but actually has remarkable toughness,
これを心血管疾患に応用する事 についてお話します
and it's no longer brittle.
実に大きな臨床上の問題だからです
And an inorganic material would normally be really brittle,
分かっている事の1つは
and you wouldn't be able to have
残念ながら 心臓発作を起こしたら
that sort of strength and toughness in it.
組織は活動停止し始めるため
One other thing I want to quickly mention is that
見通しは 時と共に 悪くなって行くかもしれません
many of the scaffolds we make are porous, and they have to be,
我々が 組織の壊死を
because you want blood vessels to grow in there.
阻止するか 再生を促すか
But the pores are actually oftentimes
どちらか出来るなら どんなにか素晴らしいことでしょう
much bigger than the cells,
今 世界中で行われている 幹細胞を使った臨床試験では
and so even though it's 3D,
あるゆるタイプの 細胞を使っていますが
the cell might see it more as a slightly curved surface,
表面化してきた共通の課題は
and that's a little bit unnatural.
細胞は心臓に移植されると 死んでしまう事が多い
And so one of the things you can think about doing
ということです
is actually making scaffolds with slightly different dimensions
細胞を心臓か
that might be able to surround your cells in 3D
血液システムに 入れる事はできますが
and give them a little bit more information.
どちらにしろ
And there's a lot of work going on in both of these areas.
十分な数の細胞を 正しい場所に入れ
Now finally, I just want to talk a little bit about
思わしい臨床結果が得られる 細胞再生ができないようなのです
applying this sort of thing to cardiovascular disease,
我々とこの分野の人々は
because this is a really big clinical problem.
その問題を解決する為の材料を 開発する事を考えています
And one of the things that we know is that,
しかし1つ違いがあります
unfortunately, if you have a heart attack,
その為には我々は 化学的技術的な向上
then that tissue can start to die,
参考となるトポグラフィー画像
and your outcome may not be very good over time.
適切な細胞を囲む方法がまだ必要です
And it would be really great, actually,
細胞はまた
if we could stop that dead tissue
伝導体のような働きを
either from dying or help it to regenerate.
するようになるでしょう
And there's lots and lots of stem cell trials going on worldwide,
なぜなら細胞そのものは よく反応し
and they use many different types of cells,
お互い同士でシグナルを 伝え合うからです
but one common theme that seems to be coming out
今でも このように
is that actually, very often, those cells will die
材料の中で細胞は 同調し合い脈打っています
once you've implanted them.
とても興奮させられる事が
And you can either put them into the heart
起きています
or into the blood system,
最後に
but either way, we don't seem to be able
この分野で働く我々に取って
to get quite the right number of cells
とても夢のある科学分野であり
getting to the location we want them to
とても夢のある科学分野であり
and being able to deliver the sort of beautiful
大なり小なり患者にインパクトを 与える可能性のあるこの分野で
cell regeneration that we would like to have
働けるという事を 本当に光栄に思います
to get good clinical outcomes.
その為にも 皆様にも感謝を述べたいと思います
And so some of the things that we're thinking of,
ありがとうございます
and many other people in the field are thinking of,
(拍手)
are actually developing materials for that.
But there's a difference here.
We still need chemistry, we still need mechanics,
we still need really interesting topography,
and we still need really interesting ways to surround the cells.
But now, the cells also
would probably quite like a material
that's going to be able to be conductive,
because the cells themselves will respond very well
and will actually conduct signals between themselves.
You can see them now
beating synchronously on these materials,
and that's a very, very exciting development
that's going on.
So just to wrap up, I'd like to actually say that
being able to work in this sort of field,
all of us that work in this field
that's not only super-exciting science,
but also has the potential
to impact on patients,
however big or small they are,
is really a great privilege.
And so for that, I'd like to thank all of you as well.
Thank you.
(Applause)