JP2002515071A - 系列限定ニューロン前駆体 - Google Patents
系列限定ニューロン前駆体Info
- Publication number
- JP2002515071A JP2002515071A JP50743099A JP50743099A JP2002515071A JP 2002515071 A JP2002515071 A JP 2002515071A JP 50743099 A JP50743099 A JP 50743099A JP 50743099 A JP50743099 A JP 50743099A JP 2002515071 A JP2002515071 A JP 2002515071A
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- cells
- neuron
- precursor cells
- cell
- population
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.哺乳動物CNSニューロン限定前駆体細胞の単離した純粋な集団。 2.ニューロン限定前駆体細胞が自己再生し得るものである、請求項1記載の 集団。 3.ニューロン限定前駆体細胞がCNSニューロン細胞には分化し得るがCN Sグリア細胞には分化し得ないものである、請求項1記載の集団。 4.ニューロン限定前駆体細胞が胎児性神経細胞接着分子を発現する、請求項 1記載の集団。 5.ニューロン限定前駆体細胞がA2B5抗体により認識されるガングリオシ ドを発現しないものである、請求項4記載の集団。 6.ニューロン限定前駆体細胞がネスチンを発現しないものである、請求項4 記載の集団。 7.ニューロン限定前駆体細胞がヒトおよび非ヒト霊長類、ウマ、イヌ、ネコ 、ウシ、ブタ、ヒツジ、ウサギ、並びにげっ歯目からなる群から選択される哺乳 動物胚から選択される、請求項1記載の集団。 8.細胞が、神経伝達物質を放出し、それに応答し得るニューロンに分化する ことの可能なものである、請求項1記載の集団。 9.ニューロンが神経伝達物質のレセプターを表示し得るものであり、また、 細胞が神経伝達物質−合成酵素を発現し得るものである、請求項8記載の集団。 10.細胞が、機能的シナプスを形成し、および/または電気的活性を発達さ せ得るニューロンに分化し得るものである、請求項1記載の集団。 11.細胞が、細胞に対する増殖因子、細胞に対する分化因子、細胞に対する 成熟因子、およびこれらのいずれかの組合わせからなる群より選択される少なく とも1つの物質を安定に発現することができるものである、請求項1記載の集団 。 12.哺乳動物CNSニューロン限定前駆体細胞の純粋な集団を単離す る方法であって、 (イ)ニューロンおよびグリア両方を生成し得る哺乳動物多分化能CNS幹細 胞集団を単離する工程、 (ロ)該多分化能CNS幹細胞を、該細胞の分化の開始を誘導するように適合 させた培地中で培養する工程、 (ハ)ニューロン限定前駆体細胞を規定する選択された抗原を発現する細胞の 亜集団を分化細胞から精製する工程、および (ニ)該細胞の精製亜集団を、その接着増殖を支持するように適合させた培地 中で培養する工程、 を含む、前記方法。 13.ニューロン限定前駆体細胞を規定する選択された抗原が胎児性神経細胞 接着分子である、請求項12記載の方法。 14.精製工程が、特異抗体捕捉、蛍光活性化細胞選別、および磁気ビーズ捕 捉からなる群より選択される手法を含む、請求項12記載の方法。 15.手法が特異抗体捕捉である、請求項14記載の方法。 16.哺乳動物多分化能CNS幹細胞が感覚上皮幹細胞である、請求項12記 載の方法。 17.CNS感覚上皮幹細胞集団を単離する工程が、 (イ)神経管の閉塞後であるが、神経管内における細胞の分化前の胚発生段階 で哺乳動物胚からCNS組織を取出すこと、 (ロ)哺乳動物胚から取出した神経管を含む細胞を解離すること、 (ハ)培養基板上において支持細胞非依存培養を行うために、解離細胞を、有 効量の線維芽細胞増殖因子とニワトリ胚抽出物を含み、感覚上皮幹細胞の接着増 殖を支持するように適合させた培地中に播種すること、および (ニ)播種した細胞を感覚上皮幹細胞の増殖に資する温度および雰囲気中でイ ンキュベートすること、 を含む、請求項16記載の方法。 18.哺乳動物胚がヒトおよび非ヒト霊長類、ウマ、イヌ、ネコ、ウシ、 ブタ、ヒツジ、ウサギ、並びにげっ歯目からなる群から選択される、請求項17 記載の方法。 19.培養基板がフィブロネクチン、ビントロネクチン、ラミニン、およびR GDペプチドからなる群から選択される、請求項17記載の方法。 20.培地が有効量の線維芽細胞増殖因子とニューロトロフィン3を含む、請 求項12記載の方法。 21.哺乳動物CNSニューロン限定前駆体細胞の純粋な集団を単離する方法 であって、 (イ)神経管の閉塞後であるが、神経管内におけるグリアおよびニューロン細 胞の分化前の胚発生段階で哺乳動物胚からCNS組織サンプルを取出す工程、 (ロ)哺乳動物胚から取出したCNS組織サンプルを含む細胞を解離する工程 、 (ハ)解離細胞から、ニューロン限定前駆体細胞を規定する選択した抗原を発 現する亜集団を精製する工程、 (ニ)培養基板上において支持細胞非依存培養を行うために、精製亜集団細胞 をニューロン限定前駆体細胞の接着増殖を支持するように適合させた培地中に播 種する工程、および (ホ)播種した細胞をニューロン限定前駆体細胞の増殖に資する温度および雰 囲気中で培養する工程、 を含むことを特徴とする、前記方法。 22.ニューロン限定前駆体細胞を規定する選択した抗原が胎児性神経細胞接 着分子である、請求項21記載の方法。 23.精製工程が、特異抗体捕捉、蛍光活性化細胞選別、および磁気ビーズ捕 捉からなる群より選択される手法を含む、請求項21記載の方法。 24.手法が特異抗体捕捉である、請求項23記載の方法。 25.哺乳動物胚がヒトおよび非ヒト霊長類、ウマ、イヌ、ネコ、ウシ、ブタ 、ヒツジ、ウサギ、並びにげっ歯目からなる群から選択される、請求項21記載 の方法。 26.請求項12記載の方法により単離された哺乳動物CNSニューロン限定 前駆体細胞の純粋な集団。 27.請求項21記載の方法により単離された哺乳動物CNSニューロン限定 前駆体細胞の純粋な集団。 28.分裂終了ニューロンの取得方法であって、 (イ)ニューロン限定前駆体細胞を供給し、増殖条件下でニューロン限定前駆 体細胞を培養する工程、および (ロ)ニューロン限定前駆体細胞の培養条件を増殖条件から分化条件に変更し 、それによってニューロン限定前駆体細胞を分裂終了ニューロンに分化させる工 程、 を含む、前記方法。 29.培養条件を変更する工程が基礎培地にレチノイン酸を添加することを含 む、請求項28記載の方法。 30.培養条件を変更する工程が基礎培地から分裂因子を除去することを含む 、請求項28記載の方法。 31.分裂因子が線維芽細胞増殖因子である、請求項30記載の方法。 32.培養条件を変更する工程が基礎培地にニューロン成熟因子を添加するこ とを含む、請求項28記載の方法。 33.ニューロン成熟因子が、ソニック・ヘッジホッグ、BMP−2、BMP −4、NT−3、NT−4、CNTF、LIF、レチノイン酸、脳由来神経向性 因子(BDNF)、および上記因子のいずれかの組合わせからなる群より選択され る、請求項32記載の方法。 34.請求項1〜7のいずれかに記載の哺乳動物CNSニューロン限定細胞を 含む単離した細胞組成物。 35.請求項34記載の組成物の治療有効量と製剤上許容し得る担体とを含む 、薬剤組成物。 36.請求項34記載の組成物の治療有効量を哺乳動物に投与する工程を含む 哺乳動物のニューロン性疾患の治療方法。 37.請求項35記載の薬剤組成物の治療有効量を哺乳動物に投与する 工程を含む哺乳動物のニューロン性疾患の治療方法。 38.組成物を筋肉内投与、鞘内投与、腹腔内投与、静脈内投与、および上記 投与のいずれかの組合わせからなる群から選択される経路にて投与する、請求項 36又は37記載の方法。 39.方法が、分化因子、増殖因子、細胞成熟因子および上記因子のいずれか の組合わせからなる群から選択されるメンバーを投与する工程を含む、請求項3 6又は37記載の方法。 40.分化因子が、レチノイン酸、BMP−2、BMP−4、および上記因子 のいずれかの組合わせからなる群から選択される、請求項39記載の方法。 41.細胞増殖因子、細胞成熟因子、細胞分化剤、および上記いずれかの組合 わせからなる群から選択される剤をグリア細胞に送達するための送達ビークルと して使用する、請求項34記載の組成物。 42.栄養性因子をニューロンに送達するための送達ビークルとして使用する 、請求項34記載の組成物。 43.哺乳動物における神経変性症候群の治療方法であって、 (イ)ニューロン限定前駆体細胞の純粋な集団を供給する工程、 (ロ)該ニューロン限定前駆体細胞を、増殖因子、神経伝達物質、神経伝達物 質合成酵素、神経ペプチド、神経ペプチド合成酵素、またはフリーラジカル介在 損傷に対する防御物質をコードする遺伝子にて、遺伝子的に形質転換し、それに よって該増殖因子、神経伝達物質、神経伝達物質合成酵素、神経ペプチド、神経 ペプチド合成酵素、またはフリーラジカル介在損傷に対する防御物質を発現する グリア限定前駆体細胞の形質転換集団を生成させる工程、および (ハ)該ニューロン限定前駆体細胞の形質転換集団の有効量を該哺乳動物に投 与する工程、 を含む、前記方法。 44.神経学的活性化合物をスクリーニングする方法であって、 (イ)in vitroで培養したニューロン限定前駆体細胞またはその誘導体 またはそれらの混合物の純粋な集団を供給する工程; (ロ)該細胞またはその誘導体またはそれらの混合物を選択した化合物に種々 の濃度で暴露する工程;および (ハ)該細胞またはその誘導体またはそれらの混合物の該選択した化合に対す る応答を、選択した時間モニターする工程; を含む、前記方法。 45.神経学的または神経変性疾患の治療方法であって、かかる治療を必要と する哺乳動物に有効量のニューロン限定前駆体細胞またはそれらの誘導体または それらの混合物を投与する工程を含む、前記方法。 46.ニューロン限定前駆体細胞またはその誘導体またはそれらの混合物を投 与するに先立って、in vitroで増殖および分化させる、請求項45記載の方法。 47.ニューロン限定前駆体細胞またはその誘導体またはそれらの混合物を投 与するに先立って、in vitroで増殖させ、次いで、投与後に、in vivoでさらに 増殖および分化させる、請求項45記載の方法。 48.ニューロン限定前駆体細胞またはその誘導体またはそれらの混合物を投 与するに先立って、in vitroで増殖させ、次いで、投与後に、in vivoで分化さ せる、請求項45記載の方法。 49.ニューロン限定前駆体細胞またはその誘導体またはそれらの混合物が異 種ドナーからのものである、請求項45記載の方法。 50.ドナーが胎児である、請求項49記載の方法。 51.ドナーが幼若体である、請求項49記載の方法。 52.ドナーが成体である、請求項49記載の方法。 53.ニューロン限定前駆体細胞またはその誘導体またはそれらの混合物が自 己由来ドナーからのものである、請求項45記載の方法。 54.ドナーが胎児である、請求項53記載の方法。 55.ドナーが幼若体である、請求項53記載の方法。 56.ドナーが成体である、請求項53記載の方法。 57.ニューロン限定前駆体細胞の誘導体がニューロン限定前駆体細胞 のin vitroでの分化により得られるものである、請求項45記載の方法。 58.ニューロン限定前駆体細胞の誘導体がニューロン限定前駆体細胞の遺伝 子形質導入により得られるものである、請求項45記載の方法。 59.哺乳動物CNSニューロン限定前駆体細胞の純粋な集団を単離する方法 であって、 (イ)哺乳動物胚幹細胞のサンプルを供給する工程、 (ロ)ニューロン限定前駆体細胞を規定する選択した抗原を発現する亜集団を 該哺乳動物胚幹細胞から精製する工程、 (ハ)培養基板上において、支持細胞非依存培養を行うために、精製亜集団細 胞を、ニューロン限定前駆体細胞の接着増殖を支持するように適合させた培地に 播種する工程、および (ニ)播種した細胞をニューロン限定前駆体細胞の増殖に資する温度および雰 囲気中でインキュベートする工程、 を含む、前記方法。
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US5087570A (en) * | 1988-05-10 | 1992-02-11 | Weissman Irving L | Homogeneous mammalian hematopoietic stem cell composition |
US5411883A (en) * | 1989-12-26 | 1995-05-02 | Somatix Therapy Corporation | Proliferated neuron progenitor cell product and process |
ES2198404T5 (es) * | 1991-07-08 | 2008-05-01 | Neurospheres Holdings Ltd. | Celulas progenitoras neurales que responden a factor de crecimiento y que se pueden hacer proliferar in vitro. |
US5175103A (en) * | 1991-10-21 | 1992-12-29 | Trustees Of University Of Pennsylvania | Preparation of pure cultures of post-mitotic human neurons |
US5589376A (en) * | 1992-07-27 | 1996-12-31 | California Institute Of Technology | Mammalian neural crest stem cells |
ATE234353T1 (de) * | 1992-10-28 | 2003-03-15 | Neurospheres Holdings Ltd | Biologische faktoren und neuronale stammzellen |
US5753505A (en) * | 1995-07-06 | 1998-05-19 | Emory University | Neuronal progenitor cells and uses thereof |
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IL133799A0 (en) | 2001-04-30 |
CA2294737A1 (en) | 1999-01-14 |
WO1999001159A1 (en) | 1999-01-14 |
AU755657B2 (en) | 2002-12-19 |
JP4371179B2 (ja) | 2009-11-25 |
KR20060002033A (ko) | 2006-01-06 |
EP1011732A4 (en) | 2002-10-23 |
AU8382398A (en) | 1999-01-25 |
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