JP5057781B2 - 修飾を組み込んだ自己集合ペプチドおよびそれを使用する方法 - Google Patents
修飾を組み込んだ自己集合ペプチドおよびそれを使用する方法 Download PDFInfo
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Description
本出願は参照により本明細書に組み込まれる発明者としてElsa Genove,Carlos SeminoおよびShuguang Zhangを列挙した2004年6月24日出願の「修飾を組み込んだ自己集合ペプチドおよびその使用方法」と題された出願の一部継続出願である(Express Mail Label No.EV416226294US、Attorney Docket Number 0492611−0574−MIT10154,USSN登録予定)。本出願は参照により本明細書に組み込まれる2003年6月25日出願の米国暫定出願60/482,261の優先権を主張する。
合衆国政府は本発明の開発において利用される補助金を提供している。特にNSFアワード番号9843342の下に全米科学財団のエンジニアリングリサーチセンタープログラムが本発明の開発を支援している。合衆国政府は本発明において特定の権利を有する。
細胞外マトリックス(ECM)はタンパク質および多糖類の両方を含む巨大分子の多様なセットよりなり、これらは細胞が生体内において存在する3次元の環境を形成し、細胞間の空隙充填物を構成している。ECMはまた組織化されて基底層または基底膜として知られるシート様の層となる。身体の多くの領域にいおいて、基底膜は上皮細胞の層または管の下部に位置(例えば内脾細胞ライニング血管)するか、または、筋肉細胞のような種々の型の個々の細胞を包囲して細胞層を相互から、または隣接する結合組織から隔たらせている場合が多い。
本発明は特にこのような必要性を意図している。本発明は自己集合ではない別のドメインを取り込むことにより自己集合ペプチドを修飾することができるがなお自己集合部分の組立を可能できるという発見を包含する。別のドメインは得られるペプチドに対して種々の特性を付与できる。好ましくは得られるペプチドは自己集合してナノ繊維を形成し、そして好ましくは巨視的構造を形成する。ペプチドの自己集合により形成される物質は特に細胞培養、組織工学および組織修復の分野において広範な用途を有する。
(I.定義)
以下の定義を本発明を理解する際に使用する。
新しい生物学的材料、特に細胞の成育、分化および生物学的機能に関する許容性物質として機能する生物学的に適合性のある材料の開発は、医療技術の進歩のため、および、細胞の生物学的特性を理解するために、広範な意味を有する。本発明は完全に合成の物質に典型的に備わっている利点を保有し、なおかつ天然原料に由来する物質の特定の望ましい特徴も保有している組成物を製造することが可能であるという認識を包含する。組成物は例えば細胞培養または組織工学、組織再生および/または修復を含む目的のため;および/または治療薬のような生物学的に活性な分子のための送達剤として、インビトロまたはインビボの何れかで使用できる。
(A.ペプチド配列および巨視的構造)
以前に記載された未修飾の自己集合ペプチドは、相補的であり構造的に適合性がある分子のファミリーを含んでいる。ペプチドおよびその特性は米国特許5,955、343および5,670,483、「組織細胞のペプチド足場封入およびその使用」と題された2001年2月6日出願の同時係争中の米国特許出願09/778200およびその他の文献に記載されている。これらの物質は種々の交互するパターンにおける親水性および疎水性のアミノ酸の反復単位よりなる。
未修飾の自己集合ペプチドまたは本発明の修飾された自己集合ペプチドの何れかから形成されたペプチドヒドロゲルは細胞および組織を培養するために種々の方法において使用してよい。細胞および組織はヒドロゲル構造の表面上で培養できる。特に理論に制約されないが、本発明者等はこのような環境は従来のプラスチックの組織培養皿のような合成の基板上の培養よりも天然の細胞の環境をより綿密に模倣していることを示唆している。ヒドロゲルが三次元の構造を形成する場合は、細胞は構造内に突起を伸長でき、或は、その内部に遊走できる。
(A.アミノ酸ドメインの付加による自己集合ペプチドの修飾)
予め識別された自己集合ペプチドは上記したとおりその自己集合を可能にする特定の構造的条件に合致する。これらの条件はペプチドの自己集合の理論的研究および多くの異なるペプチドの自己集合の挙動またはその欠如の実験的観察の両方に合致している。しかしながら、修飾を有するペプチドが自己集合する能力を排除することなく、上記した構造的条件に沿わないアミノ酸ドメインの添加によりペプチドが大きく修飾される可能性はこれまで検討されていない。
本発明は種々の比において本発明の修飾された自己集合ペプチド1つ以上に未修飾の自己集合ペプチド1つ以上を混合することができること、および、未修飾および修飾された自己集合ペプチドの両方を含む巨視的構造がこのような混合物から形成できることの認識を包含している。得られる構造は均質な自己集合ペプチド(即ち100%単一のペプチド)の自己集合により形成される構造と比較して特定の好都合な側面を有している。例えば上記したとおり、修飾された自己集合ペプチドは相当する未修飾のペプチドから形成される構造よりも弱い巨視的構造をもたらす場合があり、即ち、それらはゲル性の低い特徴を有する場合がある。しかしながら、修飾されたペプチドは所望の細胞表現型を誘導してよく、所望に応じて細胞の挙動を改変してよく、ECM分子の結合を所望に応じて改変するなどしてよい。未修飾および修飾された自己集合ペプチドの複合物(ブレンド物とも称する)から形成される巨視的構造は未修飾のペプチドの自己集合により形成された巨視的構造のものに似た機械的特性を有する場合があるが、細胞の挙動、表現方等に所望の態様で影響する能力を保有している。さらにまた修飾された自己集合ペプチドのみよりなるペプチド足場は細胞への作用の観点から旨適未満である場合がある。例えば、ゲル内の各ペプチドが修飾されている場合、得られる生物学的に活性なペプチドモチーフの濃度は所望よりも高値となり、実際は細胞の連結、増殖等を抑制するか、または、細胞に対して毒性となる場合がある。
一般的に広範な種類の異なるアミノ酸ドメインの何れも未修飾の自己集合ペプチドに付加してよいが、ただし、追加されたドメインの存在が自己集合(ナノ繊維、巨視的構造、または好ましくは両方の形成)を妨げてはならない。追加のドメインは得られるペプチドに対して多くの望ましい特性の何れかを付与してよい。例えば追加のドメインは生物学的な活性を媒介してよく、例えばペプチドの自己集合により形成される足場に接触した細胞の挙動に影響してよい。追加のドメインは天然に存在するまたは人工の生体分子、例えばECMタンパク質、細胞表面の分子、抗体等のいずれかに結合してよい。追加のドメインは金属、イオン等のような無機の物質に結合してよい。
既に発見された自己集合ペプチドを修飾するという試みは、細胞の基底膜により与えられる微小環境の重要な側面を再生する完全に合成の物質を生成したいという要望により部分的には惹起されている。細胞の基底膜はラミニン、コラーゲンおよびプロテオグリカンにより主に構成される三次元のネットワークである。基底膜は上皮細胞のシートおよびチューブに伏在し、そして筋肉細胞、脂肪細胞およびシュワン細胞のような種々の型の個々の細胞を包囲している。特定の位置(例えば肺、腎臓の糸球体)においては、基底膜は細胞のシートを分離し、フィルターとして機能する。電子顕微鏡可視化の下においては、基底膜は2つの異なる層、即ち基底膜上に静置した細胞の基底原形質膜に隣接する電子透過性の層、および、その下部の電子緻密層を含むように観察できる。基底膜はまたより下部の層を伏在する結合組織に結合させる第3の層を含む場合がある(Alberts,et al.,上記参考文献)。
et al.,1990,Sakamoto et al.,1991)。身体内の異なるECM分子の間の結合またはECM分子と非ECM分子との間の結合を媒介するペプチド配列もまた発見されている。以下のセクションはこのようなペプチドモチーフを含有および/または相互作用する種々の基底膜分子の特徴を説明するものであり、そして血管系、内皮細胞および内皮基底膜の該当する特徴をさらに詳述するものである。
本セクションは候補ペプチドが生物学的に活性なペプチドモチーフを含むかそれよりなることを調べるために使用できる種々の試験を説明する。以下に記載する試験は例示を目的とするのみであり、そして当業者は目的の細胞型および細胞の挙動に応じて、種々の別の試験および本明細書に記載した試験の変法を選択して使用できる。これらの試験のいずれにおいても、可溶性ペプチドを対照として使用できる。ある範囲のペプチド濃度(基板結合、修飾された自己集合ペプチドの部分としての存在の両方、または可溶性形態)を使用してよい。
細胞の表現型および/または機能に影響する生物学的に活性なペプチドモチーフに加えて、やはり細胞の機能に影響する種々の他の生物学的に関連のあるモチーフを未修飾の自己集合ペプチドを修飾するために使用できる。特に天然に存在するタンパク質、例えば上記したようなECMの成分(タンパク質、プロテオグリカン、GAG等)に結合することがわかっているペプチドモチーフを使用することが望ましい。特定の結合を媒介する多くのペプチドが発見されている。例えばペプチドTAGSCLRKFSTM(配列番号37)、LAGSCLSARFSTM(配列番号64)およびGEFYDLRLKGDK(配列番号65)はIV型コラーゲン中に天然に存在し、ヘパリンン特異的に結合するものとして発見されている(Koliakos,1989)。他のものは結合活性に関する合成ペプチドの系統的スクリーニング、ツーハイブリッドスクリーニング等により識別できる。
本発明の特定の実施形態においては、無機の原子または分子に結合するアミノ酸ドメインを本発明の自己集合ペプチドの非自己集合部分として使用する。多くのこのようなアミノ酸ドメインが天然に存在するタンパク質中に発見されており、多くの他のものがファージディスプレイ(後述参照)のような種々の選択手法を介して発見されている(Sarikaya,2004)。多数の他の無機結合ペプチドが知られている(Sarikaya,2004;Brown 1997;Whaley 2000等)。Au、Ag、Pt、Pd、SiO2、ZnO、CuO2、ゼオライト、CaCO3、Cr2O3、FeO3、GaAs、ZnSに結合するペプチドが発見されている。このような化合物は重金属、半導体を包含し、そして、特定の結晶構造および表面への選択的結合を示す場合すらある。これらのアミノ酸モチーフを取り込んだペプチドはナノエレクトロニクス、ナノフォトニクスおよびナノマグネティックスのような領域におけるナノテクノロジーにおいて広範に使用される(Sarikaya,2004)。このような無機結合ペプチドを含む自己集合ペプチドは自己集合がナノテクノロジーにおける基本的原理であることが広範に知られているため、特に利用性が高い。
本発明のペプチドの非自己集合部分として使用してよい別のアミノ酸ドメインを発見するための1つの方法は細胞との相互作用、特定の分子への結合等が考えられる天然に存在するタンパク質の配列から誘導した合成ペプチドを系統的にスクリーニングすることである。この方法は上記したとおり多くの生物学的に活性なペプチドを発見するために使用されている。一般的に、一緒になって配列の全部分または大部分を包含している、場合により重複しているペプチドのセットを、インビトロで合成する。次に細胞または潜在的な結合分子を個々のペプチドと接触させ、そして細胞の応答、結合の程度等を評価する。ペプチドは検出を容易にするために標識することができる。
本発明の未修飾の自己集合ペプチドまたは修飾された自己集合ペプチドまたはその組成物の何れかにより形成される構造(例えばナノ繊維、巨視的構造、ヒドロゲル)は種々の生物物理学的および工学的な手法を用いて特性化してよい。適当な手法は目視検査、円偏光二色性(CD)、動的光散乱、フーリエ変換赤外スペクトル分析(FTIR)、レオロージ試験、例えば振動レオメーター観察、原子力顕微鏡観察(ATM)、走査電子顕微鏡観察(SEM)および透過型電子顕微鏡観察(TEM)を包含する。例えば生物物理学的方法を用いてペプチド足場内のβ−シートの二次構造の程度を測定してよい。さらに、フィラメントおよび孔径、繊維の直径、長さ、弾性および容量区分を走査および透過型電子顕微鏡観察の定量的画像分析を用いて測定してよい。
本等式中、G’は材料の弾性/固体特性を示す蓄積基準である。G’’は材料の粘性/液体特性を示す損失基準である。
Press(1979))。ヒドロゲルの場合、ネットワークはかなりの量の水を保持している。
本発明の修飾された自己集合ペプチドの自己集合によるか、または、本明細書に記載した修飾または未就職の自己集合ペプチドの組み合わせの自己集合により作成されたペプチド構造は種々の組織の欠陥および疾患を治療するために使用してよい。ペプチドヒドロゲル構造は表面上に生育するか内部に封入されている細胞の有無に関わらず、例えば手術により、または、何れか他の適当な処置を用いて身体内に移植してよい。他の経路、例えば経口、経皮、筋肉内、静脈内および皮下の経路を使用してよい。当業者は適切な送達手法を選択できる。
本発明は細胞を培養するため、および/または、被験体の身体内に導入できるペプチド足場を形成するために使用してよいキットを提供する。キットは乾燥または凍結乾燥形態、溶液、または組立または部分的組立の状態で提供してよい本発明の自己集合ペプチド1つ以上を含む。キットはさらに、以下の要素、即ち、細胞の集団、細胞または組織の培養基、所定量の成長因子、所定量のイオンまたはその塩、細胞培養用の自己集合ペプチドの調製のための取扱説明書、ペプチドヒドロゲル構造の上または内部において細胞を培養するため(例えば細胞を封入するため)の取扱説明書、被験体に自己集合ペプチドを導入するための取扱説明書、細胞培養を実施する容器、ペプチドを溶解できる液体、シリンジ、ペプチドの自己集合を開始するためのイオンまたはその塩、成長因子または分化因子の1つ以上、組織培養用の培地、細胞(例えば血管内皮細胞)、対照ペプチド等の1つ以上を含んでよい。別の要素も含んでよい。
(材料および方法)
以下の材料および方法の特定のものは以下の実施例の多くに関連するものである。カタログ番号はカッコ内に示す。
PBS:リン酸塩緩衝食塩水、1mMKH2PO4、10mMNa2HPO4、137mMNaCl、2.7mMKCl、pH7.4(166789、Roche Diagnostics Corp.,IN)。
トリプシン:トリプシン−EDTA(25300−054、GibcoBRL,US)、0.05%トリプシン、HBBS中0.53mMEDTA−4Na、カルシウムおよびマグネシウム非含有、マイコプラズマ試験済み。
EGM−2:内皮半規定培地(CC−3162、Cambrex,MD)、hEGF、ヒドロコルチゾン、hFGF−B、VEGF、R3−IGF−1、アスコルビン酸、ゲンタマイシン−アンホテリン、ヘパリンおよび2%FBSのみ含有。
HAEC:ヒト大動脈内皮細胞(CC−2535、Cambrex,MD)。
トリトンX−100:Sigmaより購入(T0284,MO)。
タンパク質阻害剤カクテル:完全ミニプロテアーゼ阻害剤カクテルはRocheより購入(1836153、Indianapolis,IN)。
TNE:緩衝液、10mMトリス塩基、1mMEDTA、200mMBNaCl含有、pH7.4。
BSA:ウシ血清アルブミン(100030、Boehringer Manheim,IN)。
実施例において使用したペプチドは自己集合ペプチドRAD16−Iを基本とした。ペプチドは種々の生物学的活性を媒介するものとして予め発見されているペプチドモチーフの種々のものを含むように修飾した。ペプチドの物理化学的および構造的な特性は種々の手法を用いて評価した。ペプチドの水溶液中の溶解度を試験した。ペプチドが自己集合してより高次の構造になる能力を調べた。特に、種々の二次構造(例えばβシート)を形成するペプチドの能力は円偏光二色性を用いて測定した。ペプチドが自己集合してナノ繊維となる能力は原子間力顕微鏡(AFM)を用いて評価した。ゲルの形成は目視観察およびレオロジーにより評価した。
(材料および方法)
内皮細胞培養系。ペプチド足場(0.5%w/v)をRAD16−Iについては100%ペプチド配列において、または、3種の他の場合(YIG、RYVおよびTAG)に付き9:1の比(RAD16−I:ペプチド配列、容量/容量に基づく)でRAD16−Iと混合して、調製した。各溶液を濾過(0.2μm、Acrodyscフィルター、4192、PALL,MI)し、細胞培養チャンバーインサート(10mm直径、136935、Nalge Nunc International,IL)の上面にロード(30μl)し、層を形成させた(平均厚み=600μm)。リン酸塩緩衝食塩水(PBS)(600μl)をウェルの底部に添加し、ヒドロゲルの形成を誘導し、そして系を30分間室温でインキュベートした。PBSを培地と交換し、次にこれを新しい培地と交換した。足場を5%CO2下37℃で細胞培養インキュベーター中、内皮細胞の生育培地(EGM−2,Cambrex,MD)と共に1時間インキュベートした。
HAEC結合および単層の形成。本試験の1つの特徴は内皮細胞を培養するための合成基底膜類似物として使用される機能性付与された生体ミメティックの足場を得る可能性を検討することであった。従って実験はヒト大動脈内皮細胞(HAEC)の生育および機能を支援する指令的なマトリックスとしてペプチド足場が作用する能力を評価するために実施した。大動脈内皮細胞は通常は血管(動脈、静脈、毛細血管)および心室の内面を被覆する単層を形成するため、本発明者等は基底膜がインビボで重要な役割を果たす機能である単層の形成をペプチド足場が支援するかどうか調べた。
単層の形成を支援しなかったという事実は、生物学的に活性なモチーフの作用が濃度依存性であることを示唆している。本発明者等はペプチドの100%においてモチーフが存在することは、細胞にとって高すぎる濃度を提示し、細胞毒性をもたらしたという仮説を考えた。従って本発明者等は生物学的に活性なモチーフを取り込んだペプチドをプロトタイプのRAD16−I配列とブレンドすることにより細胞に提示される生物学的に活性なモチーフの全体的濃度を低減することに決定した。本発明者等は9:1の体積/体積比(RAD16−I:生物学的に活性なペプチドモチーフを含む修飾ペプチド配列、ペプチドはw/w基準で等濃度となるように溶解した)を選択し、未修飾および修飾ペプチドがこの比で存在する溶液からペプチド足場を生成した。ゲルの形成および様相の目視による観察および足場の取り扱いおよび操作中に観察された特徴に基づけば、本発明者等は複合足場の機械的特性はRAD16−Iより完全になる足場のものと極めて似ていると結論した。この所見は、未修飾ペプチドの修飾ペプチドに対する適切な比を選択することにより足場の機械的特性が調節できることを示している。
(材料および方法)
NO放出の測定。酸化窒素(NO)の放出はGreiss法により窒素酸化物(NOx)を測定することにより調べた。慨すれば、培地を培養第3日後にウシ胎児血清(FBS)またはアスコルビン酸を含有しない新しい培地と交換した。翌日、市販のキット(482702、Calbiochem,CA)を用いて、製造元の説明書に従って培地を検査することによりNO放出を分析した。各条件を3連で試験した。
図11A〜11HはHAECによる低密度リポタンパク質(LDL)の取り込みおよびDAPI染色を示す。LDLは血管内皮細胞のマーカーとして一般的に使用されており、細胞がその血管内皮の表現型を修飾ペプチド足場上で保持していることを確認するものである。DAPI染色は細胞の核を可視化するために使用した。
Claims (31)
- 自己集合ペプチドを含む、足場を形成するための組成物であって、該自己集合ペプチドは、以下:
(a)自己集合を媒介する第1のアミノ酸ドメインであって、ここで該ドメインは、相補的であり、構造的に適合性があり、そして未修飾形態で存在する場合には自己集合して巨視的構造となる、交互する疎水性および親水性のアミノ酸を含む、第1のアミノ酸ドメイン;および
(b)単離された形態で自己集合しない第2のアミノ酸ドメインであって、ここで、該第2のアミノ酸ドメインの配列が、配列番号33、配列番号35および配列番号37からなる群より選択される配列を含む、第2のアミノ酸ドメイン;
を含み、
該第1および第2のアミノ酸ドメインが、ペプチド結合により結合しており、
該ペプチドは、溶液中の唯一のペプチドとして存在する場合に自己集合し、そして、該自己集合ペプチドを構成するアミノ酸の総数が、8〜36アミノ酸である、
組成物。 - 前記第1および第2のアミノ酸ドメインが、相互に共有結合的または非共有結合的に交差結合している、請求項1に記載の組成物。
- 前記第1のアミノ酸ドメインが、複数のRADAペプチドサブユニットを含む、請求項1に記載の組成物。
- 前記第1のアミノ酸ドメインが、RADA16−Iペプチドを含む、請求項1に記載の組成物。
- 前記第2のアミノ酸ドメインが、単離された形態で存在する場合は自己集合しないが、前記ペプチドが自己集合して巨視的構造を形成するように前記第1のアミノ酸ドメインの集合を可能にする、請求項1に記載の組成物。
- 前記第2のアミノ酸ドメインが、単離された形態で存在する場合は自己集合しないが、前記ペプチドが自己集合してナノ繊維を形成するように前記第1のアミノ酸ドメインの集合を可能とする、請求項1に記載の組成物。
- 前記ペプチドが、直鎖である、請求項1に記載の組成物。
- 前記ペプチドが、分枝鎖である、請求項1に記載の組成物。
- 自己集合ペプチドを含む、足場を形成するための組成物であって、該自己集合ペプチドは、以下:
(a)自己集合を媒介する第1のアミノ酸ドメインであって、ここで該ドメインは、相補的であり、構造的に適合性があり、そして未修飾形態で存在する場合には自己集合して巨視的構造となる、交互する疎水性および親水性のアミノ酸を含む、第1のアミノ酸ドメイン;および
(b)単離された形態で自己集合しない第2のアミノ酸ドメインであって、ここで、該第2のアミノ酸ドメインの配列が、配列番号33、配列番号35および配列番号37からなる群より選択される配列を含む、第2のアミノ酸ドメイン;
を含み、
該第1および第2のアミノ酸ドメインが、リンカードメインにより結合しており、
該ペプチドは、溶液中の唯一のペプチドとして存在する場合に自己集合し、そして、該自己集合ペプチドを構成するアミノ酸の総数が、8〜36アミノ酸である、
組成物。 - 前記リンカードメインが、1つ以上のグリシン残基を含む、請求項9に記載の組成物。
- 前記第1のアミノ酸ドメインが複数のRADAペプチドサブユニットを含む、請求項9に記載の組成物。
- 前記第1のアミノ酸ドメインがRADAペプチド16−Iペプチドを含む、請求項9に記載の組成物。
- 前記第2のアミノ酸ドメインが、単離された形態で存在する場合は自己集合しないが、前記ペプチドが自己集合して巨視的構造を形成するように前記第1のアミノ酸ドメインの集合を可能にする、請求項9に記載の組成物。
- 前記ペプチドが、直鎖である、請求項9に記載の組成物。
- 前記ペプチドがヒドロゲルを形成するように自己集合する、請求項1に記載の組成物。
- 請求項1に記載の組成物を含む足場であって、前記自己集合ペプチドは、自己集合したものである、足場。
- 前記足場の表面に結合するか、または、該足場内に封入された複数の細胞をさらに含む、請求項16に記載の足場。
- 前記細胞が、軟骨細胞、骨髄細胞、骨細胞、骨膜細胞、軟骨膜細胞、線維芽細胞、ニューロン細胞、海馬細胞、表皮細胞、内皮細胞、上皮細胞、ケラチノサイト、基底細胞、棘状細胞、顆粒細胞、胚性幹細胞、卵巣細胞、膵臓細胞、頚部細胞、肝細胞、包皮細胞、好中球、リンパ球、マクロファージ、樹状細胞または前述の細胞型のいずれかの前駆体からなる群より選択される、請求項17に記載の足場。
- 前記足場が3次元である、請求項16に記載の足場。
- 細胞を培養するための足場であって、
請求項16に記載の足場に細胞を接触させること、および、細胞培養に適した条件下で、一定期間該足場を維持することを含む、足場。 - 前記細胞が、前記足場の表面で培養される、請求項16に記載の足場。
- 前記細胞が、三次元に配置された足場の内部に封入される、請求項16に記載の足場。
- 前記細胞が、前記足場内に均一に分布している、請求項22に記載の足場。
- 前記細胞が、軟骨細胞、骨髄細胞、骨細胞、骨膜細胞、軟骨膜細胞、線維芽細胞、ニューロン細胞、海馬細胞、表皮細胞、内皮細胞、上皮細胞、ケラチノサイト、基底細胞、棘状細胞、顆粒細胞、胚性幹細胞、卵巣細胞、膵臓細胞、頚部細胞、肝細胞、包皮細胞、好中球、リンパ球、マクロファージ、樹状細胞または前述の細胞型のいずれかの前駆体からなる群より選択される、請求項23に記載の足場。
- キットであって、以下:
(a)請求項1に記載の組成物;
(b)巨視的構造への前記ペプチドの自己集合を開始するための取扱説明書;および、
(c)細胞の集団、細胞または組織の培養培地、所定量の成長因子、所定量のイオンまたはその塩、細胞培養用の該組成物の調製のための取扱説明書、ペプチドヒドロゲル構造の上または内部において細胞を培養するための取扱説明書、被験体に該組成物を導入するための取扱説明書、細胞培養を実施し得る容器、該ペプチドを溶解し得る液体、シリンジ、ペプチドの自己集合を開始するためのイオンまたはその塩、および、一種以上の成長因子または分化因子からなる群より選択される少なくとも1つの要素、
を備える、キット。 - 請求項9に記載の組成物を含む足場であって、前記自己集合ペプチドが自己集合したものである、足場。
- 前記足場の表面に結合するか、または、該足場内に封入された複数の細胞をさらに含む、請求項26に記載の足場。
- 前記細胞が、軟骨細胞、骨髄細胞、骨細胞、骨膜細胞、軟骨膜細胞、線維芽細胞、ニューロン細胞、海馬細胞、表皮細胞、内皮細胞、上皮細胞、ケラチノサイト、基底細胞、棘状細胞、顆粒細胞、胚性幹細胞、卵巣細胞、膵臓細胞、頚部細胞、肝細胞、包皮細胞、好中球、リンパ球、マクロファージ、樹状細胞または前述の細胞型のいずれかの前駆体からなる群より選択される、請求項27に記載の足場。
- 前記足場が3次元である、請求項26に記載の足場。
- 細胞を培養するための足場であって、
請求項26に記載の足場に細胞を接触させること、および、細胞培養に適した条件下で、一定期間該足場を維持することを含む、足場。 - 前記第1のアミノ酸ドメインを構成するアミノ酸の総数が、8アミノ酸〜16アミノ酸の間である、請求項1〜9のいずれかに記載の組成物。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015099083A1 (ja) | 2013-12-25 | 2015-07-02 | 日産化学工業株式会社 | 血清および血液を固化する水分散液 |
EP4286397A1 (en) | 2022-06-01 | 2023-12-06 | ETH Zurich | Hydrogel-forming proteins |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006014570A2 (en) | 2004-07-06 | 2006-02-09 | 3D Matrix, Inc. | Purified amphilic peptide compositions and uses thereof |
US8039258B2 (en) | 2004-09-28 | 2011-10-18 | Ethicon, Inc. | Tissue-engineering scaffolds containing self-assembled-peptide hydrogels |
JP2008526749A (ja) * | 2005-01-04 | 2008-07-24 | ザ ブライハム アンド ウイメンズ ホスピタル, インコーポレイテッド | 自己アセンブリするペプチドナノファイバーを用いたpdgfの徐放性の送達 |
KR20100102750A (ko) * | 2005-04-25 | 2010-09-24 | 메사추세츠 인스티튜트 오브 테크놀로지 | 지혈 및 다른 생리학적 활성을 촉진하기 위한 조성물 및 방법 |
US9162005B2 (en) | 2005-04-25 | 2015-10-20 | Arch Biosurgery, Inc. | Compositions for prevention of adhesions and other barrier applications |
DE102005021435A1 (de) * | 2005-05-04 | 2006-11-09 | Universitätsklinikum Freiburg | Verfahren zur serum-/proteinfreien Kultur von Stamm- und Progenitorzellen |
JP2006346420A (ja) * | 2005-06-13 | 2006-12-28 | Univ Nagoya | 移植材料及び骨質改善剤 |
WO2007000979A1 (ja) * | 2005-06-27 | 2007-01-04 | Menicon Co., Ltd. | 自己組織化ペプチドおよびそれより得られるゲル |
JP2007039394A (ja) * | 2005-08-04 | 2007-02-15 | Nippon Menaade Keshohin Kk | 老化予防改善皮膚外用剤 |
US8647867B2 (en) | 2005-09-30 | 2014-02-11 | National University Corportion Okayama University | Cell cultivation method and cell culture |
JP4982841B2 (ja) * | 2005-10-12 | 2012-07-25 | 国立大学法人名古屋大学 | 再生医療骨組成物 |
GB2433506A (en) * | 2005-12-20 | 2007-06-27 | Sharp Kk | A method of producing a multimeric capture agent |
JP2007217376A (ja) * | 2006-02-17 | 2007-08-30 | Nagoya Institute Of Technology | 自己組織化ペプチド組成物 |
JP2007217375A (ja) * | 2006-02-17 | 2007-08-30 | Nagoya Institute Of Technology | 自己組織化ペプチド |
JP2009535338A (ja) | 2006-04-25 | 2009-10-01 | マサチューセッツ・インスティテュート・オブ・テクノロジー | 汚染因子、体液または他の実体の動きに影響を及ぼし、そして/あるいは他の生理学的状態に影響を及ぼすための組成物および方法 |
JP5496671B2 (ja) * | 2006-09-26 | 2014-05-21 | マサチューセッツ インスティテュート オブ テクノロジー | 修飾自己組織化ペプチド |
WO2008073392A2 (en) * | 2006-12-11 | 2008-06-19 | 3D Matrix, Inc. | Compositions and methods for cardiac tissue protection and regeneration |
DK2146733T3 (da) * | 2007-03-14 | 2021-01-11 | Arch Biosurgery Inc | Treatment of leaky or damaged tight junctions and enhancing extracellular matrix |
ES2534770T3 (es) * | 2007-12-05 | 2015-04-28 | 3-D Matrix, Ltd. | Material para la curación de heridas y la reconstrucción de la piel |
CA2716752A1 (en) * | 2008-02-29 | 2009-09-03 | Showa University | Method for producing artificial skin |
SG194405A1 (en) * | 2008-10-06 | 2013-11-29 | 3 D Matrix Ltd | Tissue occluding agent |
US9084752B2 (en) * | 2009-12-14 | 2015-07-21 | The University Of Hong Kong | Compositions and methods for controlling proliferation and differentiation of cells |
WO2011072482A1 (en) | 2009-12-14 | 2011-06-23 | The University Of Hong Kong | Nano cancer barrier device(ncbd) to immobilize and inhibit the division of metastic cancer stem cells |
US8741833B2 (en) | 2010-07-16 | 2014-06-03 | Massachusetts Institute Of Technology | Self-assembling peptides incorporating modifications and methods of use thereof |
JP5855651B2 (ja) * | 2010-07-16 | 2016-02-09 | マサチューセッツ インスティテュート オブ テクノロジー | 改変を組み込んだ自己組織化ペプチドおよびその使用方法 |
US10793307B2 (en) | 2012-07-06 | 2020-10-06 | 3-D Matrix, Ltd. | Fill-finish process for peptide solutions |
US9241891B2 (en) | 2012-10-30 | 2016-01-26 | The Procter & Gamble Company | Personal care compositions comprising self-assembling peptides |
JP6502352B2 (ja) | 2013-08-22 | 2019-04-17 | アーチ・バイオサージェリー・インコーポレイテッド | 流体の移動を制御するための移植可能なメッシュ |
AU2015229549B2 (en) | 2014-03-10 | 2019-05-23 | 3-D Matrix, Ltd. | Self-assembling peptide compositions |
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Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL85372A (en) * | 1987-02-12 | 1992-12-01 | Us Health | Penta to nona-peptides with laminin - like activity having an amino acid sequence and anti- metastatic compositions containing them |
US5955343A (en) | 1992-12-28 | 1999-09-21 | Massachusetts Institute Of Technology | Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor |
US5670483A (en) | 1992-12-28 | 1997-09-23 | Massachusetts Insititute Of Technology | Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor |
EP1250463B1 (en) * | 2000-01-24 | 2006-04-05 | Compound Therapeutics, Inc. | Sensitive, multiplexed diagnostic assays for protein analysis |
WO2002062961A2 (en) * | 2001-02-06 | 2002-08-15 | Massachusetts Institute Of Technology | Peptide scaffold encapsulation of tissue cells and uses thereof |
WO2003046560A2 (en) * | 2001-11-30 | 2003-06-05 | National Research Council Of Canada | Self-assembly molecules |
WO2003070749A2 (en) * | 2002-02-15 | 2003-08-28 | Northwestern University | Self-assembly of peptide-amphiphile nanofibers under physiological conditions |
AU2003249606A1 (en) | 2002-05-13 | 2003-12-02 | Massachusetts Institute Of Technology | Angiogenesis and cardiac tissue engineering with peptide hydrogels and related compositions and methods of use thereof |
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- 2004-06-25 WO PCT/US2004/020549 patent/WO2005014615A2/en active Application Filing
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WO2015099083A1 (ja) | 2013-12-25 | 2015-07-02 | 日産化学工業株式会社 | 血清および血液を固化する水分散液 |
EP4286397A1 (en) | 2022-06-01 | 2023-12-06 | ETH Zurich | Hydrogel-forming proteins |
WO2023232843A1 (en) | 2022-06-01 | 2023-12-07 | Eth Zurich | Hydrogel-forming proteins |
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EP2711025A3 (en) | 2014-09-10 |
JP2011046741A (ja) | 2011-03-10 |
WO2005014615A3 (en) | 2009-03-26 |
DK1636250T3 (en) | 2016-02-22 |
EP1636250A2 (en) | 2006-03-22 |
EP1636250B1 (en) | 2016-01-06 |
EP1636250A4 (en) | 2010-11-03 |
JP2007526232A (ja) | 2007-09-13 |
EP2711025A2 (en) | 2014-03-26 |
WO2005014615A2 (en) | 2005-02-17 |
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