JP2004149534A - 活性な治療薬または物質による組織内における一定の標的領域に対する胚芽幹細胞のホーミング - Google Patents
活性な治療薬または物質による組織内における一定の標的領域に対する胚芽幹細胞のホーミング Download PDFInfo
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Abstract
【解決手段】 上記方法は一定の組織における標的領域に一定のサイトカイン、ケモキネシスまたは化学誘引物質等のような一定の転座刺激因子を配給する工程、および種々のヒト胚芽幹細胞を上記哺乳類動物に導入してこれらのヒト胚芽幹細胞を上記組織の標的領域に対してホーミング処理することにより当該標的領域において脈管増殖を行なう工程を含む。
【選択図】 図1
Description
本発明は一般に侵襲性の心臓治療のための種々の方法および装置を含む細胞に基づく治療法に関連しており、特に、心臓虚血の最少侵襲性の治療のための方法および装置に関連している。
心臓の一室内に挿入されて心臓壁部に治療用薬物を投与するためのカテーテルと、
心臓壁部の厚さに応じて信号を発生するセンサーと、
上記センサーから信号を受信して心臓壁部の厚さに応じて治療を制御するコントローラにより構成されている。
カテーテルを心臓の一室内に導入する工程と、
上記カテーテルの位置座標を感知する工程と、
上記座標を用いて所望部位における心臓壁部に係合した状態で上記カテーテルを位置決めする工程と、
上記カテーテルを用いて上記部位に治療用薬物を投与する工程により構成されている。
心臓の壁部の厚さにおける変化を示す信号を受信する工程と、
上記厚さの変化に応じて心臓壁部における一定部位に治療用薬物を投与する工程により構成されている。
本発明の目的において、用語の「治療用薬物(therapeutic drug)」は新脈管形成に利用される細胞を含む。当該技術分野において既に確立されているように、筋芽細胞または筋細胞のような細胞、特に心筋細胞が種々の形態の病気を治療するために遺伝子またはそのプロモータのような組換え分子を伝達するために利用される。治療用物質を配給するための発現ベクターのような配給ビヒクルとしての細胞の使用が本明細書に参考文献として含まれる米国特許第5,602,301号(フィールド,ローレン(Field, Loren))およびPCT出願公開第WO 96/18303号(ロー,ピーター(Law, Peter))に記載されている。すなわち、上記の点について、筋芽細胞または筋細胞は全般的な遺伝子導入ビヒクルとして利用されて、心臓組織のような組織に直接的に配給される。従って、筋芽細胞または筋細胞は組織に治療作用を与える組換えタンパク質およびその他の分子のような治療用物質を最終的に発現するための発現ベクターとして使用される。例えば、このような治療作用の一例は増殖因子またはその他のタンパク質のような脈管形成因子を発現する要因となる配給ビヒクルとして筋芽細胞または筋細胞を利用することである。これらの増殖因子はさらに副行血管を形成して組織における新脈管形成を生じる要因となる。さらに、これらの副行血管は塩基性および酸性の線維芽増殖因子(FGF)、形質転換増殖因子(TGF)、脈管内皮増殖因子(VEGF)等のような脈管形成因子により形成される。この種の治療手法は改善された血流を必要とする組織または器官に対して明らかに有利である。例えば、この手法の応用は心臓組織における脈管再生において特に有用である。
本発明の目的において、用語の「治療用薬物」は筋発生のために移植できる任意の種類の細胞も含む。筋芽細胞または筋細胞のような細胞が細胞の移植により筋発生を促進するために使用できることが知られている。このような特別の技法が本明細書に参考文献として含まれるPCT出願公開第WO 96/18303号(ロー,ピーター(Law, Peter))および米国特許第5,602,301号(フィールド,ローレン(Field, Loren))において記載されている。細胞移植による筋発生を有効にするために、別の細胞と融合できる細胞を特定して利用することが重要である。
上記の細胞治療技法を有効に配備するために、薬物配給システム48(図4)、およびLMRおよび配給システム96(図9)が特にこの目的に対して有用である。例えば、細胞はカテーテル20(図1および図2)、カテーテル45(図3)、およびカテーテル64(図6)により配給される。既に説明したように、生存度マップはそれぞれ当該生存度マップを作成するためのシステム48またはシステム96を用いて作成される。さらに、心臓の生存度マップは制御回路52により作成されてディスプレイ58上に表示される。表示された生存度マップの有用な目的の一つは、例えば、まだ生存可能であって治療を必要としている心臓組織の領域のような心臓組織における虚血領域を特定することである。加えて、生存度マップは心筋梗塞に罹った領域および瘢痕領域並びに心臓内における解剖構造学的な目標を特定するためにも有用である。システム48およびシステム96は目標の治療計画の一部分として生存度マップ上に点の格子を決定して標識するための回路52を用いることにより当該目標の治療計画の効果的な組み立てを着実に可能にする。従って、医者は点から点の間隔の間に所望密度の細胞配給を計画することができる。
本発明による上記の方法およびシステムはまた組織内の一定の標的領域に対する種々のサイトカイン媒介型および/または化学誘引物質媒介型の細胞の転座にも関連している。このように転座処理された細胞はその患者(哺乳類動物)に対して生体内で配給される種々の前駆体細胞である。なお、以下において定められているように、用語の「前駆体細胞(precursor cell)」は一定の自己由来細胞または一定のドナーから由来している細胞(ドナー前駆体細胞)のいずれかを含む任意の種類の細胞を意味する。ドナー前駆体細胞はまた一定の同種異系の供給源から由来している種々の細胞も含み、これらの細胞はヒト胚芽幹細胞(hES)並びに一定の異種供給源から由来している種々の細胞を含む。このような異種のドナー前駆体細胞は、マロウフ(Malouf)他(「アダルト−デライブド・ステム・セルズ・フロム・ザ・リバー・ビカム・マイオサイツ・イン・ザ・ハート・イン・ビボ(Adult-Derived Stem Cells from the Liver become Myocytes in the Heart in Vivo)」,アメリカン・ジャーナル・オブ・パソロジー(American Journal of Pathology),158巻,6号,2001年6月,1929頁乃至1934乃至)により利用されているWB−F344成人幹細胞系等のような、成人の肝組織から由来している成人幹細胞を含む間葉組織および種々の器官から由来している細胞等のような異種の成人幹細胞を含む。加えて、上記用語の「前駆体細胞(precursor cell)」はさらに一定の胚芽幹細胞(hESまたは異種胚芽幹細胞)から由来している一定の血管芽細胞または一定の血管芽細胞様細胞として分類されている任意の細胞として定義される。このような血管芽細胞様細胞は種々の内皮先祖細胞(EPCs)、すなわち、種々の血管芽細胞、造血幹細胞(HSCs)、および骨髄由来幹細胞(BMSCs)およびその他の成人幹細胞を含む。従って、本発明によれば、上記において定められている全ての細胞型が上記「前駆体細胞(precursor cell)」の定義に含まれると考えられる。
(1)さらに、脈管形成により脈管増殖を行なう処理を含む請求項1に記載の方法。
(2)さらに、血管形成により脈管増殖を行なう処理を含む請求項1に記載の方法。
(3)さらに、動脈形成により脈管増殖を行なう処理を含む請求項1に記載の方法。
(4)さらに、種々のヒト胚芽幹細胞を遺伝子工学的に処理して一定の治療用のタンパク質を生成する処理を含む請求項1に記載の方法。
(5)さらに、VEGF、GM−CSF、bFGF、PDGF、IGF−1、PLGF、SDF−1、ANG1、ANG2、TIE2、HGF、TNFα、TGFβ、SCGF、セレクチン、インテグリン、MMP、PECAM、カドヘリン、NO、CXC、MCP−1、HIFα、COX−2およびこれらの全ての異性体または類似体から成る群からの少なくとも1種類の転座刺激因子を配給する処理を含む請求項1に記載の方法。
(7)さらに、前記転座刺激因子の注入において一定のカテーテルを使用する処理を含む実施態様(6)に記載の方法。
(8)さらに、前記カテーテル上における一定の位置センサーを用いて前記標的領域に前記カテーテルを操縦する処理を含む実施態様(7)に記載の方法。
(9)さらに、心臓における一定の心筋層の中に前記転座刺激因子を注入する処理を含む実施態様(7)に記載の方法。
(10)さらに、心臓における一定の心外膜の中に前記転座刺激因子を注入する処理を含む実施態様(7)に記載の方法。
(12)さらに、心臓における一定の脈管の壁部の中に前記転座刺激因子を注入する処理を含む実施態様(7)に記載の方法。
(13)さらに、生活能力について前記組織をマッピング処理することにより前記標的領域を確認する処理を含む請求項1に記載の方法。
(14)さらに、一定の電極を有する一定のカテーテルを用いて生活能力について前記組織をマッピングする処理を含む実施態様(13)に記載の方法。
(15)さらに、前記カテーテル上における一定の位置センサーを用いて前記カテーテルを操縦する処理を含む実施態様(14)に記載の方法。
(17)さらに、前記組織の標的領域の近くに前記ヒト胚芽幹細胞を導入する処理を含む請求項1に記載の方法。
(18)種々のヒト胚芽幹細胞を遺伝子工学的に処理して一定の治療用のタンパク質を生成する処理を含む請求項2に記載の方法。
(19)さらに、VEGF、GM−CSF、bFGF、PDGF、IGF−1、PLGF、SDF−1、ANG1、ANG2、TIE2、HGF、TNFα、TGFβ、SCGF、セレクチン、インテグリン、MMP、PECAM、カドヘリン、NO、CXC、MCP−1、HIFα、COX−2およびこれらの全ての異性体または類似体から成る群からの少なくとも1種類の転座刺激因子を配給する処理を含む請求項2に記載の方法。
(20)さらに、注入により前記組織の標的領域に前記転座刺激因子を配給する処理を含む請求項2に記載の方法。
(22)さらに、前記カテーテル上における一定の位置センサーを用いて前記標的領域に前記カテーテルを操縦する処理を含む実施態様(21)に記載の方法。
(23)さらに、心臓における一定の心筋層の中に前記転座刺激因子を注入する処理を含む実施態様(21)に記載の方法。
(24)さらに、心臓における一定の心外膜の中に前記転座刺激因子を注入する処理を含む実施態様(21)に記載の方法。
(25)さらに、心臓における一定の脈管の中に前記転座刺激因子を注入する処理を含む実施態様(21)に記載の方法。
(27)さらに、生活能力について前記組織をマッピング処理することにより前記標的領域を確認する処理を含む請求項2に記載の方法。
(28)さらに、一定の電極を有する一定のカテーテルを用いて生活能力について前記組織をマッピングする処理を含む実施態様(27)に記載の方法。
(29)さらに、前記カテーテル上における一定の位置センサーを用いて前記カテーテルを操縦する処理を含む実施態様(28)に記載の方法。
(30)さらに、静脈内投与により前記ヒト胚芽幹細胞を導入する処理を含む請求項2に記載の方法。
(32)種々のヒト胚芽幹細胞を遺伝子工学的に処理して一定の治療用のタンパク質を生成する処理を含む請求項3に記載の方法。
(33)さらに、VEGF、GM−CSF、bFGF、PDGF、IGF−1、PLGF、SDF−1、ANG1、ANG2、TIE2、HGF、TNFα、TGFβ、SCGF、セレクチン、インテグリン、MMP、PECAM、カドヘリン、NO、CXC、MCP−1、HIFα、COX−2およびこれらの全ての異性体または類似体から成る群からの少なくとも1種類の転座刺激因子を配給する処理を含む請求項3に記載の方法。
(34)さらに、注入により前記組織の標的領域に前記転座刺激因子を配給する処理を含む請求項3に記載の方法。
(35)さらに、前記転座刺激因子の注入において一定のカテーテルを使用する処理を含む実施態様(34)に記載の方法。
(37)さらに、心臓における一定の心筋層の中に前記転座刺激因子を注入する処理を含む実施態様(35)に記載の方法。
(38)さらに、心臓における一定の心外膜の中に前記転座刺激因子を注入する処理を含む実施態様(35)に記載の方法。
(39)さらに、心臓における一定の脈管の中に前記転座刺激因子を注入する処理を含む実施態様(35)に記載の方法。
(40)さらに、心臓における一定の脈管の壁部の中に前記転座刺激因子を注入する処理を含む実施態様(35)に記載の方法。
(42)さらに、一定の電極を有する一定のカテーテルを用いて生活能力について前記組織をマッピングする処理を含む実施態様(41)に記載の方法。
(43)さらに、前記カテーテル上における一定の位置センサーを用いて前記カテーテルを操縦する処理を含む実施態様(42)に記載の方法。
(44)さらに、静脈内投与により前記ヒト胚芽幹細胞を導入する処理を含む請求項3に記載の方法。
(45)さらに、前記組織の標的領域の近くに前記ヒト胚芽幹細胞を導入する処理を含む請求項3に記載の方法。
(47)さらに、VEGF、GM−CSF、bFGF、PDGF、IGF−1、PLGF、SDF−1、ANG1、ANG2、TIE2、HGF、TNFα、TGFβ、SCGF、セレクチン、インテグリン、MMP、PECAM、カドヘリン、NO、CXC、MCP−1、HIFα、COX−2およびこれらの全ての異性体または類似体から成る群からの少なくとも1種類の転座刺激因子を配給する処理を含む請求項4に記載の方法。
(48)さらに、注入により前記組織の標的領域に前記転座刺激因子を配給する処理を含む請求項4に記載の方法。
(49)さらに、前記転座刺激因子の注入において一定のカテーテルを使用する処理を含む実施態様(48)に記載の方法。
(50)さらに、前記カテーテル上における一定の位置センサーを用いて前記標的領域に前記カテーテルを操縦する処理を含む実施態様(49)に記載の方法。
(52)さらに、心臓における一定の心外膜の中に前記転座刺激因子を注入する処理を含む実施態様(49)に記載の方法。
(53)さらに、心臓における一定の脈管の中に前記転座刺激因子を注入する処理を含む実施態様(49)に記載の方法。
(54)さらに、心臓における一定の脈管の壁部の中に前記転座刺激因子を注入する処理を含む実施態様(49)に記載の方法。
(55)さらに、生活能力について前記組織をマッピング処理することにより前記標的領域を確認する処理を含む請求項4に記載の方法。
(57)さらに、前記カテーテル上における一定の位置センサーを用いて前記カテーテルを操縦する処理を含む実施態様(56)に記載の方法。
(58)さらに、静脈内投与により前記ヒト胚芽幹細胞を導入する処理を含む請求項4に記載の方法。
(59)さらに、前記組織の標的領域の近くに前記ヒト胚芽幹細胞を導入する処理を含む請求項4に記載の方法。
(60)さらに、心臓における2個以上の室部の中の生活能力についてマッピングする処理を含む実施態様(14)に記載の方法。
(62)さらに、一定の高速マッピング技法により前記組織をマッピングする処理を含む実施態様(60)に記載の方法。
(63)さらに、6個乃至10個の点を用いて一定の生活能力マップを形成する処理を含む実施態様(62)に記載の方法。
(64)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(63)に記載の方法。
(65)さらに、一定の高速マッピング技法を用いて前記組織をマッピングする処理を含む実施態様(14)に記載の方法。
(67)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(66)に記載の方法。
(68)さらに、心臓における2個以上の室部の中の生活能力について前記組織をマッピングする処理を含む実施態様(28)に記載の方法。
(69)さらに、二心室マッピング処置を行なう処理を含む実施態様(68)に記載の方法。
(70)さらに、一定の高速マッピング技法により前記組織をマッピングする処理を含む実施態様(68)に記載の方法。
(72)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(71)に記載の方法。
(73)さらに、一定の高速マッピング技法を用いて前記組織をマッピングする処理を含む実施態様(28)に記載の方法。
(74)さらに、6個乃至10個の点を用いて一定の生活能力マップを形成する処理を含む実施態様(73)に記載の方法。
(75)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(74)に記載の方法。
(77)さらに、二心室マッピング処置を行なう処理を含む実施態様(76)に記載の方法。
(78)さらに、一定の高速マッピング技法により前記組織をマッピングする処理を含む実施態様(76)に記載の方法。
(79)さらに、6個乃至10個の点を用いて一定の生活能力マップを形成する処理を含む実施態様(78)に記載の方法。
(80)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(79)に記載の方法。
(82)さらに、6個乃至10個の点を用いて一定の生活能力マップを形成する処理を含む実施態様(81)に記載の方法。
(83)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(82)に記載の方法。
(84)さらに、心臓における2個以上の室部の中の生活能力について前記組織をマッピングする処理を含む実施態様(56)に記載の方法。
(85)さらに、二心室マッピング処置を行なう処理を含む実施態様(84)に記載の方法。
(87)さらに、6個乃至10個の点を用いて一定の生活能力マップを形成する処理を含む実施態様(86)に記載の方法。
(88)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(87)に記載の方法。
(89)さらに、一定の高速マッピング技法を用いて前記組織をマッピングする処理を含む実施態様(56)に記載の方法。
(90)さらに、6個乃至10個の点を用いて一定の生活能力マップを形成する処理を含む実施態様(89)に記載の方法。
(91)さらに、3個程度の少ない点を用いて前記生活能力マップを形成する処理を含む実施態様(90)に記載の方法。
24 針
30 移動機構
32 位置センサー
36 接触センサー
38 電極
40 針センサー
45 カテーテル
47 螺旋状の針
48 配給システム
50 制御コンソール
52 制御回路
54 ディスペンサ
58 ディスプレイ
60 トランスデューサ
64 カテーテル
78 カテーテル
80 導波管
82 光学装置
88 カプセル
94 レーザー供給源
96 LMRおよび配給システム
Claims (4)
- 一定の哺乳類動物の組織内における脈管増殖を誘発するための方法において、
(a)前記組織の一定の標的領域に対して一定の転座刺激因子を配給する工程、および
(b)種々のヒト胚芽幹細胞を前記哺乳類動物に導入して当該ヒト胚芽幹細胞をその組織の標的領域に対してホーミング処理することにより当該標的領域において脈管増殖を行なう工程を含む方法。 - 一定の哺乳類動物の組織内における筋発生を誘発するための方法において、
(a)前記組織の一定の標的領域に対して一定の転座刺激因子を配給する工程、および
(b)種々のヒト胚芽幹細胞を前記哺乳類動物に導入して当該ヒト胚芽幹細胞をその組織の標的領域に対してホーミング処理することにより当該標的領域において筋発生を行なう工程を含む方法。 - 一定の哺乳類動物の組織内における再造形を誘発するための方法において、
(a)前記組織の一定の標的領域に対して一定の転座刺激因子を配給する工程、および
(b)種々のヒト胚芽幹細胞を前記哺乳類動物に導入して当該ヒト胚芽幹細胞をその組織の標的領域に対してホーミング処理することにより当該標的領域において再造形を行なう工程を含む方法。 - 一定の哺乳類動物の組織内における一定の瘢痕を置換するための方法において、
(a)一定の標的領域として前記瘢痕を設定する工程、
(b)前記組織の標的領域に対して一定の転座刺激因子を配給する工程、および
(c)種々のヒト胚芽幹細胞を前記哺乳類動物に導入して当該ヒト胚芽幹細胞をその組織の標的領域に対してホーミング処理することにより当該標的領域における前記瘢痕の置換を行なう工程を含む方法。
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US10/281,709 US20030113303A1 (en) | 1998-02-05 | 2002-10-28 | Homing of embryonic stem cells to a target zone in tissue using active therapeutics or substances |
Publications (1)
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JP2004149534A true JP2004149534A (ja) | 2004-05-27 |
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JP2003366451A Pending JP2004149534A (ja) | 2002-10-28 | 2003-10-27 | 活性な治療薬または物質による組織内における一定の標的領域に対する胚芽幹細胞のホーミング |
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US (1) | US20030113303A1 (ja) |
EP (1) | EP1415661A1 (ja) |
JP (1) | JP2004149534A (ja) |
KR (1) | KR20040038758A (ja) |
AU (1) | AU2003255219A1 (ja) |
CA (1) | CA2447199A1 (ja) |
IL (1) | IL158543A0 (ja) |
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JP2015097835A (ja) * | 2008-10-10 | 2015-05-28 | ミルックス・ホールディング・エスエイ | 薬剤の注入 |
JP2013529932A (ja) * | 2010-07-01 | 2013-07-25 | リジェネレイティブ リサーチ ファウンデーション | 持続放出組成物を用いる未分化細胞培養方法 |
US9994826B2 (en) | 2010-07-01 | 2018-06-12 | Regenerative Research Foundation | Methods for culturing undifferentiated cells using sustained release compositions |
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US20030113303A1 (en) | 2003-06-19 |
EP1415661A1 (en) | 2004-05-06 |
AU2003255219A1 (en) | 2004-05-13 |
CA2447199A1 (en) | 2004-04-28 |
KR20040038758A (ko) | 2004-05-08 |
IL158543A0 (en) | 2004-05-12 |
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