Molly Stevens: A new way to grow bone

モリー・スティーブンス: 新しい骨再生法

翻訳: Reiko Bovee 校正: Eriko T

As humans, it's in our nature

誰もが 健康を改善したり

to want to improve our health and minimize our suffering.

肉体的苦しみを最小限に留め

Whatever life throws at us,

我が身に起る事が

whether it's cancer, diabetes, heart disease,

癌 糖尿病 心臓病または骨折と

or even broken bones, we want to try and get better.

それが何であろうと 良くなりたいと思うものです

Now I'm head of a biomaterials lab,

私は生体材料研究所の所長ですが

and I'm really fascinated by the way that humans

過去 様々な材料が 独創的な方法で人体に

have used materials in really creative ways

使われてきたということに

in the body over time.

とても感心させられます

Take, for example, this beautiful blue nacre shell.

例えば この貝の青い真珠層をご覧下さい

This was actually used by the Mayans

これはマヤ族が歯のインプラントに

as an artificial tooth replacement.

実際 使っていました

We're not quite sure why they did it.

その理由はよく分かりませんが

It's hard. It's durable.

硬く長持ちし

But it also had other very nice properties.

他にもとても良い特質があります

In fact, when they put it into the jawbone,

顎に入れると

it could integrate into the jaw,

顎骨と融合するのです

and we know now with very sophisticated

高度画像技術で

imaging technologies

分かっている

that part of that integration comes from the fact

融合の理由は この材料の

that this material is designed

用途によく合ったデザイン

in a very specific way, has a beautiful chemistry,

そして素晴らしい化学的性質と

has a beautiful architecture.

構造にありました

And I think in many ways we can sort of think

あらゆる意味で

of the use of the blue nacre shell and the Mayans

マヤ族の青い真珠層を持つ貝の使い道は

as the first real application

まさしく最初の

of the bluetooth technology.

ブルートゥース技術だ なんて思ったりします

(Laughter)

（笑）

But if we move on and think throughout history

先に進んで 歴史を通して

how people have used different materials in the body,

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

very often it's been physicians

創意工夫をしてきたのは 医師の場合が多く

that have been quite creative.

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,

but the very interesting thing about it

興味深いことに

was that material, actually, wasn't causing

その物質は炎症反応を

any inflammatory response.

全く引き起こしていなかったのでした

So he looked into this, and he figured out

調べて分かったことは

that actually that material was little shards of plastic

その物質は 小さなプラスチックのかけらで

that were coming from the canopy of the Spitfires.

スピットファイア戦闘機の天蓋から 来る物でした

And this led him to propose that material

それで彼はこの物質を

as a new material for intraocular lenses.

新しい眼内レンズの素材 として提唱したのです

It's called PMMA, and it's now used

PMMAと呼ばれるもので

in millions of people every year

毎年 何百万人の人の目に

and helps in preventing cataracts.

白内障を防ぐ為に使われています

And that example, I think, is a really nice one,

この例は

because it helps remind us that in the early days,

昔は機械的機能をさせる為に

people often chose materials

よく生体不活性材料が 選ばれ

because they were bioinert.

Their very purpose was to perform a mechanical function.

使われていた ということを 示しています

You'd put them in the body

生体不活性材料を体に入れても

and you wouldn't get an adverse response.

拒絶反応はありません

And what I want to show you is that

しかし ここで私が述べたい事は

in regenerative medicine,

再生医療は

we've really shifted away from that idea

生体不活性材料から

of taking a bioinert material.

全く離れたということです

We're actually actively looking for materials

我々が積極的に探している材料は

that will be bioactive, that will interact with the body,

生体と作用する 生体活性材料で

and that furthermore we can put in the body,

生体内に入れられると

they'll have their function,

そこで機能し

and then they'll dissolve away over time.

時が経つにつれ 生体内に吸収されるものです

If we look at this schematic,

このチャートをご覧下さい

this is showing you what we think of

これが示しているのは

as the typical tissue-engineering approach.

細胞組織工学の 典型的アプローチです

We have cells there, typically from the patient.

普通患者から細胞を取り

We can put those onto a material,

それを材料に入れ

and we can make that material very complex if we want to,

非常に複雑なものに することもでき—

and we can then grow that up in the lab

実験室で増殖するか

or we can put it straight back into the patient.

患者の体に直接 戻すか どちらでもできます

And this is an approach that's used all over the world,

これが世界中で そして

including in our lab.

我々の実験室でも 行われている方法です

But one of the things that's really important

幹細胞について 本当に大切なことの１つは

when we're thinking about stem cells

is that obviously stem cells can be many different things,

幹細胞は あらゆる組織に分化でき

and they want to be many different things,

又 そうなる傾向にあるので

and so we want to make sure that the environment

幹細胞を入れる環境に

we put them into has enough information

我々が必要な情報を 確実に組み込むと

so that they can become the right sort

目的の特定の組織に なるという事です

of specialist tissue.

And if we think about the different types of tissues

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

that people are looking at regenerating

all over the world, in all the different labs in the world,

there's pretty much every tissue you can think of.

殆ど考え得る全ての組織 と言っていい程です

And actually, the structure of those tissues

そんな組織の構造は

is quite different, and it's going to really depend

かなり多様で

on whether your patient has any underlying disease,

患者の他の 隠れた病気とか健康問題が

other conditions, in terms of how

you're going to regenerate your tissue,

組織の再生法や

and you're going to need to think about the materials

材料の使用法や

you're going to use really carefully,

their biochemistry, their mechanics,

生化学的性質､ 機能

and many other properties as well.

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

Our tissues all have very different abilities to regenerate,

組織は其々 異なる再生能力があります

and here we see poor Prometheus,

ここで思い出すのが 可哀想なプロメテウス

who made a rather tricky career choice

危なっかしい決断をした彼は

and was punished by the Greek gods.

ギリシャの神々に罰せられ

He was tied to a rock, and an eagle would come

岩に縛り付けられ 鷲が毎日

every day to eat his liver.

彼の肝臓をついばみに来ます

But of course his liver would regenerate every day,

彼の肝臓は毎日再生し

and so day after day he was punished

そうやって来る日も来る日も

for eternity by the gods.

永遠に神々に罰せられるのです

And liver will regenerate in this very nice way,

肝臓はこのように 再生されることになるでしょうが

but actually if we think of other tissues,

他の組織

like cartilage, for example,

例えば軟骨は

even the simplest nick and you're going to find it

どんな些細な欠損でも

really difficult to regenerate your cartilage.

再生するのは とても難しいのです

So it's going to be very different from tissue to tissue.

この様に組織により 違いが非常に大きく

Now, bone is somewhere in between,

骨の再生能力はその中間です

and this is one of the tissues that we work on a lot in our lab.

骨は我々の実験室で よく扱われる組織の１つで

And bone is actually quite good at repairing.

自己修復能力は 実は かなり高いのです

It has to be. We've probably all had fractures

そうでなければ困ります たぶん我々はみな

at some point or other.

骨折を経験しているでしょうし

And one of the ways that you can think

骨折治療の１つの方法は

about repairing your fracture

is this procedure here, called an iliac crest harvest.

「腸骨採取」と呼ばれる手法で

And what the surgeon might do

外科医が

is take some bone from your iliac crest,

腸骨から骨を採取し

which is just here,

ここにありますが—

and then transplant that somewhere else in the body.

体の他の部分にそれを移植します

And it actually works really well,

これは本当にうまく行くのです

because it's your own bone,

本人の骨なので

and it's well vascularized,

うまく血管新生化し

which means it's got a really good blood supply.

血液の流れが とても良くなるのですが

But the problem is, there's only so much you can take,

問題は採骨できる量に 限界があるという事です

and also when you do that operation,

その上 手術後 採骨した場所が

your patients might actually have significant pain

２年経っても

in that defect site even two years after the operation.

非常に痛む可能性があるのです

So what we were thinking is,

それで我々が考えた事は

there's a tremendous need for bone repair, of course,

勿論 骨修復の需要は 非常に大きいのですが—

but this iliac crest-type approach

腸骨タイプのアプローチでは

really has a lot of limitations to it,

限界があまりにあるので

and could we perhaps recreate

必要に応じ 生体内で

the generation of bone within the body

骨を再生し 移植したらどうだろう

on demand and then be able to transplant it

それにより腸骨採取後のような

without these very, very painful aftereffects

極度の痛みが伴わない移植が

that you would have with the iliac crest harvest?

出来るのではないだろうか？ ということです

And so this is what we did, and the way we did it

その我々のやり方は

was by coming back to this typical tissue-engineering approach

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 actually thinking about it rather differently.

かなり違った観点を取りました

And we simplified it a lot,

随分 簡素化して

so we got rid of a lot of these steps.

かなりステップを省きました

We got rid of the need to harvest cells from the patient,

患者からの 細胞採取の必要性

we got rid of the need to put in really fancy chemistries,

あらゆる高価な 化学薬品の必要性

and we got rid of the need

そして研究室で担体を

to culture these scaffolds in the lab.

培養する必要性を なくしました

And what we really focused on

我々が本当に 焦点を置いているのは

was our material system and making it quite simple,

材料系と それを簡素化する事ですが

but because we used it in a really clever way,

よく考えられた方法で使用したので

we were able to generate enormous amounts of bone

このアプローチによって

using this approach.

膨大な量の骨を 再生できたのです

So we were using the body

それで我々は生体を

as really the catalyst to help us

骨を大量に作る為の

to make lots of new bone.

媒体として使いました

And it's an approach that we call

そのアプローチを

the in vivo bioreactor, and we were able to make

「生体バイオリアクター」と呼び このやり方で

enormous amounts of bone using this approach.

とてつもない量の骨を 再生できるのです

And I'll talk you through this.

分かり易く説明すると

So what we do is,

こうです

in humans, we all have a layer of stem cells

生体には幹細胞の層が

on the outside of our long bones.

長骨の外側にあり

That layer is called the periosteum.

「骨膜」とよばれ

And that layer is actually normally

普段とても

very, very tightly bound to the underlying bone,

しっかりと その下の骨に密着していて

and it's got stem cells in it.

幹細胞を含んでいます

Those stem cells are really important

この幹細胞は

in the embryo when it develops,

胎芽の成長にとても重要で

and they also sort of wake up if you have a fracture

骨折すると

to help you with repairing the bone.

骨を修復しようと活性化します

So we take that periosteum layer

我々はその骨膜に目をつけ

and we developed a way to inject underneath it

その下に液体を 注入する方法を開発しました

a liquid that then, within 30 seconds,

その液体は注入後30秒内で

would turn into quite a rigid gel

固形のゲルになり

and can actually lift the periosteum away from the bone.

骨から骨膜を持ち上げる事ができ

So it creates, in essence, an artificial cavity

人工の空洞が

that is right next to both the bone

骨と幹細胞豊かな骨膜の間にできます

but also this really rich layer of stem cells.

And we go in through a pinhole incision

微小な切り口から入るので

so that no other cells from the body can get in,

生体の他の細胞は入れません

and what happens is that that artificial in vivo bioreactor cavity

人工的に作られた空洞 バイオリアクター・スペースが

can then lead to the proliferation of these stem cells,

幹細胞の増殖に繋がり

and they can form lots of new tissue,

多くの新しい組織を作り

and then over time, you can harvest that tissue

時が経つと組織を採取し

and use it elsewhere in the body.

人体の他の場所に移植できます

This is a histology slide

これがそのプロセスで見られる

of what we see when we do that,

組織構造のスライドです

and essentially what we see

我々が見ているのは

is very large amounts of bone.

非常に大量の骨です

So in this picture, you can see the middle of the leg,

この写真では足の中の中央部—

so the bone marrow,

骨髄が右端に見え

then you can see the original bone,

次に本来の骨があり

and you can see where that original bone finishes,

その骨が終わった所の

and just to the left of that is the new bone

丁度左に新生骨が

that's grown within that bioreactor cavity,

バイオリアクター・スペース内で 再生しています

and you can actually make it even larger.

もっと大きくもできます

And that demarcation that you can see

本来の骨と新生骨との

between the original bone and the new bone

境界部分は

acts as a very slight point of weakness,

ほんの少しだけですが弱い所で

so actually now the surgeon can come along,

ここが外科医の出番です

can harvest away that new bone,

新生骨を採取し

and the periosteum can grow back,

骨膜が再生します

so you're left with the leg

初めっから手術など

in the same sort of state

しなかったような状態の

as if you hadn't operated on it in the first place.

足が戻ってきます

So it's very, very low in terms of after-pain

それで術後の痛みは

compared to an iliac crest harvest.

腸骨採集後と比べれば とても軽いのです

And you can grow different amounts of bone

骨再生量は

depending on how much gel you put in there,

ゲルの注入量次第なので

so it really is an on demand sort of procedure.

必要に応じて調節できます

Now, at the time that we did this,

我々が これを公表した時

this received a lot of attention in the press,

メディアの注目を浴びました

because it was a really nice way

新しい骨再生の

of generating new bone,

実にいい方法だからです

and we got many, many contacts

これを使いたいと言う

from different people that were interested in using this.

様々な人々から問い合わせが来ました

And I'm just going to tell you,

実のところ

sometimes those contacts are very strange,

全くおかしなものもありました

slightly unexpected,

思ってもなかったような

and the very most interesting,

とっても面白いもの

let me put it that way, contact that I had,

と言ったらいいでしょう

was actually from a team of American footballers

その１つは 米国のフットボール選手からで

that all wanted to have double-thickness skulls

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

made on their head.

And so you do get these kinds of contacts,

こんな問い合わせは 本当にあるのです

and of course, being British

フランスで育った

and also growing up in France,

イギリス人の私は

I tend to be very blunt,

ちょっと辛口な傾向があり

and so I had to explain to them very nicely

彼らにこう説明しました

that in their particular case,

「あなた達の様な特殊ケースでは

there probably wasn't that much in there

たぶんその中にはあまり

to protect in the first place.

守るものなんて ないんじゃないの」って

(Laughter)

（笑）

(Applause)

（拍手）

So this was our approach,

これが我々のアプローチでした

and it was simple materials,

単純な材料ですが

but we thought about it carefully.

入念に計画しました

And actually we know that those cells

生体や胎芽の幹細胞が

in the body, in the embryo, as they develop

成長すると

can form a different kind of tissue, cartilage,

ある異なる組織の 軟骨になるのが分かっているので

and so we developed a gel that was slightly different

少し化学的性質の違うゲルを開発し

in nature and slightly different chemistry,

put it in there, and we were able to get

それを注入し軟骨を100%

100 percent cartilage instead.

再生できました

And this approach works really well, I think,

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

for pre-planned procedures,

but it's something you do have to pre-plan.

前もって計画しなければ ならないものです

So for other kinds of operations,

他の手術では

there's definitely a need for other

他の担体を基礎とした アプローチが確かに必要です

scaffold-based approaches.

And when you think about designing

他の担体を開発する時は

those other scaffolds, actually,

you need a really multi-disciplinary team.

様々な分野からの 専門家チームが必要です

And so our team has chemists,

我々のチームには化学者

it has cell biologists, surgeons, physicists even,

細胞生物学者 外科医 そして物理学者さえもが加わり

and those people all come together

皆で一体となり

and we think really hard about designing the materials.

材料の開発に懸命に 取り組んでいます

But we want to make them have enough information

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

that we can get the cells to do what we want,

but not be so complex as to make it difficult

材料には 十分な情報を

to get to clinic.

備えて欲しいのです

And so one of the things we think about a lot

我々の仕事の１つは

is really trying to understand

生体組織構造の理解を 深める事です

the structure of the tissues in the body.

And so if we think of bone,

骨について考えると

obviously my own favorite tissue,

私が関心を持つ組織ですが—

we zoom in, we can see,

ズームインしてみると

even if you don't know anything about bone structure,

皆さんが骨組織の事は よく知らなくても

it's beautifully organized, really beautifully organized.

本当に素晴らしく 組織化されていると分かります

We've lots of blood vessels in there.

そこには血管が張り巡っています

And if we zoom in again, we see that the cells

更にズームインすると

are actually surrounded by a 3D matrix

ナノスケール繊維の

of nano-scale fibers, and they give a lot

３D基質が細胞を囲み

of information to the cells.

細胞に多くの情報を与えています

And if we zoom in again,

更にズームインすると

actually in the case of bone, the matrix

骨の場合 細胞周辺の基質は美しく

around the cells is beautifully organized

ナノスケールで纏まり

at the nano scale, and it's a hybrid material

混成された

that's part organic, part inorganic.

有機・無機質のハイブリッドです

And that's led to a whole field, really,

ここで全く新しい分野

that has looked at developing materials

ハイブリッド的な構造を持った 材料の開発分野に移り

that have this hybrid kind of structure.

And so I'm showing here just two examples

その例を２つだけお見せします

where we've made some materials that have that sort of structure,

ハイブリッド的構造を持った

and you can really tailor it.

調整可能な材料を作りました

You can see here a very squishy one

ここにブヨブヨした物が見えますが

and now a material that's also this hybrid sort of material

これもハイブリッド的材料で

but actually has remarkable toughness,

驚く程強く

and it's no longer brittle.

壊れ易くありません

And an inorganic material would normally be really brittle,

無機質の材料は通常とても脆く

and you wouldn't be able to have

このような丈夫さや強さはありません

that sort of strength and toughness in it.

One other thing I want to quickly mention is that

もう１つだけちょっと 触れておきたい事は

many of the scaffolds we make are porous, and they have to be,

我々が作る担体の多くは

because you want blood vessels to grow in there.

そこに血管が通り 育つように多孔質です

But the pores are actually oftentimes

穴のサイズは

much bigger than the cells,

細胞より大きく

and so even though it's 3D,

３Dではありますが

the cell might see it more as a slightly curved surface,

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

and that's a little bit unnatural.

少々不自然です

And so one of the things you can think about doing

ですから 考えないといけないのは

is actually making scaffolds with slightly different dimensions

担体を少し違う次元で

that might be able to surround your cells in 3D

３Dで細胞を包み

and give them a little bit more information.

もう少し情報を 細胞に与えるように作る事です

And there's a lot of work going on in both of these areas.

これらの領域では 色々な研究がなされています

Now finally, I just want to talk a little bit about

最後に少しだけ

applying this sort of thing to cardiovascular disease,

これを心血管疾患に応用する事 についてお話します

because this is a really big clinical problem.

実に大きな臨床上の問題だからです

And one of the things that we know is that,

分かっている事の１つは

unfortunately, if you have a heart attack,

残念ながら 心臓発作を起こしたら

then that tissue can start to die,

組織は活動停止し始めるため

and your outcome may not be very good over time.

見通しは 時と共に 悪くなって行くかもしれません

And it would be really great, actually,

我々が 組織の壊死を

if we could stop that dead tissue

阻止するか 再生を促すか

either from dying or help it to regenerate.

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

And there's lots and lots of stem cell trials going on worldwide,

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 they use many different types of cells,

あるゆるタイプの 細胞を使っていますが

but one common theme that seems to be coming out

表面化してきた共通の課題は

is that actually, very often, those cells will die

細胞は心臓に移植されると 死んでしまう事が多い

once you've implanted them.

ということです

And you can either put them into the heart

細胞を心臓か

or into the blood system,

血液システムに 入れる事はできますが

but either way, we don't seem to be able

どちらにしろ

to get quite the right number of cells

十分な数の細胞を 正しい場所に入れ

getting to the location we want them to

and being able to deliver the sort of beautiful

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

cell regeneration that we would like to have

to get good clinical outcomes.

And so some of the things that we're thinking of,

我々とこの分野の人々は

and many other people in the field are thinking of,

are actually developing materials for that.

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

But there's a difference here.

しかし１つ違いがあります

We still need chemistry, we still need mechanics,

その為には我々は 化学的技術的な向上

we still need really interesting topography,

参考となるトポグラフィー画像

and we still need really interesting ways to surround the cells.

適切な細胞を囲む方法がまだ必要です

But now, the cells also

細胞はまた

would probably quite like a material

伝導体のような働きを

that's going to be able to be conductive,

するようになるでしょう

because the cells themselves will respond very well

なぜなら細胞そのものは よく反応し

and will actually conduct signals between themselves.

お互い同士でシグナルを 伝え合うからです

You can see them now

今でも このように

beating synchronously on these materials,

材料の中で細胞は 同調し合い脈打っています

and that's a very, very exciting development

とても興奮させられる事が

that's going on.

起きています

So just to wrap up, I'd like to actually say that

最後に

being able to work in this sort of field,

この分野で働く我々に取って

all of us that work in this field

とても夢のある科学分野であり

that's not only super-exciting science,

とても夢のある科学分野であり

but also has the potential

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

to impact on patients,

however big or small they are,

働けるという事を 本当に光栄に思います

is really a great privilege.

And so for that, I'd like to thank all of you as well.

その為にも 皆様にも感謝を述べたいと思います

Thank you.

ありがとうございます

(Applause)

（拍手）