KR970706490A - 중추신경계 기능 및 기능부전의 실험실 모델(in vitro models of cns function and dysfunction) - Google Patents
중추신경계 기능 및 기능부전의 실험실 모델(in vitro models of cns function and dysfunction)Info
- Publication number
- KR970706490A KR970706490A KR1019970701845A KR19970701845A KR970706490A KR 970706490 A KR970706490 A KR 970706490A KR 1019970701845 A KR1019970701845 A KR 1019970701845A KR 19970701845 A KR19970701845 A KR 19970701845A KR 970706490 A KR970706490 A KR 970706490A
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- disease
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- 210000003169 central nervous system Anatomy 0.000 title 2
- 230000004064 dysfunction Effects 0.000 title 2
- 238000010874 in vitro model Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 29
- 239000003124 biologic agent Substances 0.000 claims abstract 15
- 208000012902 Nervous system disease Diseases 0.000 claims abstract 14
- 208000025966 Neurological disease Diseases 0.000 claims abstract 11
- 239000001963 growth medium Substances 0.000 claims abstract 11
- 230000000694 effects Effects 0.000 claims abstract 8
- 239000003102 growth factor Substances 0.000 claims abstract 7
- 210000003061 neural cell Anatomy 0.000 claims abstract 4
- 210000001178 neural stem cell Anatomy 0.000 claims abstract 3
- 210000004027 cell Anatomy 0.000 claims description 17
- 230000001537 neural effect Effects 0.000 claims description 12
- 210000002569 neuron Anatomy 0.000 claims description 12
- 210000001130 astrocyte Anatomy 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 239000002243 precursor Substances 0.000 claims 7
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 6
- 210000003494 hepatocyte Anatomy 0.000 claims 6
- 210000000130 stem cell Anatomy 0.000 claims 5
- 239000002299 complementary DNA Substances 0.000 claims 4
- 208000024827 Alzheimer disease Diseases 0.000 claims 3
- 201000010374 Down Syndrome Diseases 0.000 claims 3
- 208000018737 Parkinson disease Diseases 0.000 claims 3
- 206010044688 Trisomy 21 Diseases 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 210000004498 neuroglial cell Anatomy 0.000 claims 3
- 108090000623 proteins and genes Proteins 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 235000003170 nutritional factors Nutrition 0.000 claims 2
- 230000004069 differentiation Effects 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 abstract 1
- 238000012258 culturing Methods 0.000 abstract 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 4
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 4
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 4
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- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
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- 230000024245 cell differentiation Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
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- 230000035755 proliferation Effects 0.000 description 1
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Abstract
중식되고 있거나 중식된 신경간세포 및 이들의 후손세포가 신경발달 및 기능화의 연구, 및 새로운 치료 및 그밖의 생물학적 작용제의 CNS 효과를 측정하기 위한 CNS 모델 시스템을 생산하는데 사용된다. 신경간세포는 출생전후의 환자로부터의 소량의 정상 또는 질병감염된 CNS 조직에서 얻는다. 본 발명은 다양성이 한정되도록 클론적으로 유도될수 있는 다량의 조직이 소량의 CNS 조지으로부터 생성되게 한다. 본 발명에서는 신경 간세포의 분화된 후손세포가 뉴우런, 성상세포 및 회소돌기아교세포를 포함한 다양한 형태의 CNS 세포를 포함하도록 하는 CNSS 모델 시스템이 기재되어 있다. 신경 또는 그밖의 생물학적 작용제의 효과를 스크리닝하고, 다역가 신경간세포 및 정상 또는 질병 감염된 공여체의 간세포 유도된 후손세포에서의 유전자 발현을 분석하는 것은 본 발명의 모델 시스템을 이용하여 수행할 수 있다.
Description
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제1도는 표피 성장인자(EGF) 반응성 세포의 증식을 도시한 도면, 제2도는 단일의 EGF-발생 구체로부터 뉴우런, 성상세포 및 회소돌기아교세포로 세포분화가 일어나는 것을 도시한 도면, 제3도는 성상세포 선조체와 함께 배양된 신경구체(neurosphere)의 표지화를 도시한 도면, 제4도는 뇌로부터 유래된 신경 항성인자(BDNF)의 존재하에 1개의 신경구체로부터 제조된 뉴우런 수적 증가를 나타낸 도면, 제5도는 BDNF의 존재하에 증강된 신경처리 과정의 부산물을 도시한 도면, 제6도는 1개의 신경구체내에서 선택된 수의 세포에 의한 BDNF에 대한 반응을 도시한 도면.
Claims (36)
- a) 하나 이상의 다역가 간세포를 함유하는 포유동물 신경조직을 분리하는 단계; b) 하나 이상의 성장인자를 함유하는 배양배지에서 다역가 간세포를 증식시켜 증식된 전구세포의 배양물을 얻는 단계; c) 증식된 전구 세포를 생물학적 작용제와 접촉시키는 단계; 및 d) 전구세포에 대한 생물학적 작용제의 효과를 측정하는 단계를 포함하여, 신경 전구 세로에 대한 하나 이상의 생물학적 작용제의 효과를 측정하는 방법.
- 제1항에 있어서, 성장인자가 EGF, bFGF, 및 EFG와 bFGF의 복합물로 이루어진 군중에서 선택됨을 특징으로 하는 방법.
- 제1항에 있어서, 배양배지가 한정됨을 특징으로 하는 방법.
- 제1항에 있어서, 포유동물 신경조직을 출생 후의 포유동물에서 얻음을 특징으로 하는 방법.
- 제1항에 있어서, 포유동물 신경조직을 사람 공여체에서 얻음을 특징으로 하는 방법.
- 제5항에 있어서, 사람의 신경질환 또는 질병을 앓고 있음을 특징으로 하는 방법.
- 제6항에 있어서, 생물학적 작용제가 신경질환 또는 질병에 효능적인 치료제임을 특징으로 하는 방법.
- 제7항에 있어서, 신경질환 또는 질병이 알쯔하이머 질환, 파킨슨 질환, 및 다운 증후군으로 이루어진 군중에서 선택됨을 특징으로 하는 방법.
- 제1항 또는 제6항에 있어서, 단계 (d)의 효과가 생물학적 작용제와 접촉되는 단계(c)의 증식된 전구세포의 유전자 라이브레리를 생물학적 작용제와 접촉되지 않은 단계(b)의 증식된 전구세포의 유전자 라이브레리와 비교함으로써 측정됨을 특징으로 하는 방법.
- a) 하나 이상의 다역가 간세포를 함유하는 포유동물 신경조직을 분리하는 단계; b) 하나 이상의 성장인자를 함유하는 제1배양배지에서 다역가 간세포를 증식시켜 증식된 전구세포의 배양물을 얻는 단계; c) 증식된 전구세포를 유도하여 생물학적 작용제의 존재하에 제2배양배지에서 분화시키는 단계; 및 d) 전구세포의 분화에 대한 생물학적 작용제의 효과를 측정하는 단계를 포함하여, 신경 전구세포에 대한 하나 이상의 생물학적 작용제의 효과를 측정하는 방법.
- 제10항에 있어서, 성장인자가 EGF, bFGF, 및 EFG와 bFGF의 복합물로 이루어진 군중에서 선택됨을 특징으로 하는 방법.
- 제10항에 있어서, 제1배양배지가 한정됨을 특징으로 하는 방법.
- 제10항에 있어서, 포유동물 신경조직을 소아 또는 성숙한 포유동물에서 얻음을 특징으로 하는 방법.
- 제10항에 있어서, 포유동물 신경조직을 사람 공여체에서 얻음을 특징으로 하는 방법.
- 제14항에 있어서, 사람의 신경질환 또는 질병을 앓고 있음을 특징으로 하는 방법.
- 제15항에 있어서, 생물학적 작용제가 신경질환 또는 질병에 효능적인 치료제임을 특징으로 하는 방법.
- 제16항에 있어서, 신경질환 또는 질병이 알쯔하이머 질환, 파킨슨 질환, 및 다운 증후군으로 이루어진 군중에서 선택됨을 특징으로 하는 방법.
- 제10항 또는 제15항에 있어서, 단계 (d)의 효과가 생물학적 작용제와 접촉되는 단계(c)의 증식된 전구세포의 유전자 라이브레리를 생물학적 작용제와 접촉되지 않은 단계(b)의 증식된 전구세포의 유전자 라이브레리와 비교함으로써 측정됨을 특징으로 하는 방법.
- 제10항에 있어서, 증식된 전구세포를 유도하고 영양인자의 존재하에 분화시켜 분화된 세포의 표현형을 조작하는 것을 특징으로 하는 방법.
- 제10항에 있어서, 제2배양배지가 신경교 세포 공급자-세포층을 포함함을 특징으로 하는 방법.
- a) 하나 이상의 다역가 간세포를 함유하는 포유동물 신경조직을 분리하는 단계; b) 하나 이상의 성장인자를 함유하는 제1배양배지에서 다역가 간세포를 증식시켜 증식된 전구세포의 배양물을 얻는 단계; c) 분화된 신경세포의 배양물을 얻도록 증식된 전구세포를 유도하여 제2배양배지에서 분화시키는 단계; d) 분화된 신경세포를 생물학적 작용제와 접촉시키는 단계; 및 e) 분화된 신경세포에 대한 생물학적 작용제의 효과를 측정하는 단계를 포함하여, 신경 전구세포에 대한 하나 이상의 생물학적 작용제의 효과를 측정하는 방법.
- 제21항에 있어서, 성장인자가 EGF, bFGF, 및 EFG와 bFGF의 복합물로 이루어진 군중에서 선택됨을 특징으로 하는 방법.
- 제21항에 있어서, 배양배지가 한정됨을 특징으로 하는 방법.
- 제21항에 있어서, 포유동물 신경조직을 소아 또는 성인으로부터 얻음을 특징으로 하는 방법.
- 제21항에 있어서, 포유동물 신경조직을 사람 공여체에서 얻음을 특징으로 하는 방법.
- 제25항에 있어서, 사람의 신경질환 또는 질병을 앓고 있음을 특징으로 하는방법.
- 제26항에 있어서, 생물학적 작용제가 신경질환 또는 질병에 효능적인 치료제임을 특징으로 하는 방법.
- 제26항에 있어서, 신경질환 또는 질병이 알쯔하이머 질환, 파킨슨 질환, 및 다운 증후군으로 이루어진 군중에서 선택됨을 특징으로 하는 방법.
- 제21항 또는 제26항에 있어서, 단계 (e)의 효과가 생물학적 작용제와 접촉되는 단계(d)에서의 분화된 신경세포의 유전자 라이브레리를 생물학적 작용제와 접촉되지 않은 단계(c)에서의 분화된 신경 세포의 유전자 라이브레리와 비교함으로써 측정됨을 특징으로 하는 방법.
- 제21항에 있어서, 증식된 전구세포를 유도하고 영양인자의 존재하에 분화시켜 분화된 세포의 표현형을 조작함을 특징으로 하는 방법.
- 제21항에 있어서, 제2의 배양배지가 신경교 세포 공급자-세포층을 포함함을 특징으로 하는 방법.
- 신경세포로부터 제조된 cDNA 라이브레리.
- 제32항에 있어서, 신경세포가 신경 간세포임을 특징으로 하는 cDNA 라이브레리.
- 제32항에 있어서, 신경세포가 전구세포임을 특징으로 하는 cDNA 라이브레리.
- 제32항에 있어서, 신경세포가 뉴우런, 성상세포 및 희소돌기아교세포로 이루어진 군중에서 선택된 분화된-세포임을 특징으로 하는 cDNA 라이브레리.
- 제32항에 있어서, 신경세포가 신경질환 또는 질병을 앓고 있는 사람으로부터 유도됨을 특징으로 하는 cDNA 라이브레리.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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PCT/CA1995/000542 WO1996009543A1 (en) | 1994-09-23 | 1995-09-22 | In vitro models of cns function and dysfunction |
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KR1019970701845A KR970706490A (ko) | 1994-09-23 | 1995-09-22 | 중추신경계 기능 및 기능부전의 실험실 모델(in vitro models of cns function and dysfunction) |
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EP (2) | EP1130394B1 (ko) |
JP (1) | JPH10505754A (ko) |
KR (1) | KR970706490A (ko) |
AT (2) | ATE345496T1 (ko) |
AU (1) | AU714837B2 (ko) |
CA (1) | CA2200709A1 (ko) |
DE (2) | DE69535300T2 (ko) |
DK (2) | DK1130394T3 (ko) |
ES (1) | ES2167461T3 (ko) |
FI (1) | FI971168A (ko) |
MX (1) | MX9702126A (ko) |
NO (1) | NO971245L (ko) |
PT (1) | PT783693E (ko) |
WO (1) | WO1996009543A1 (ko) |
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US5753506A (en) * | 1996-05-23 | 1998-05-19 | Cns Stem Cell Technology, Inc. | Isolation propagation and directed differentiation of stem cells from embryonic and adult central nervous system of mammals |
US7544511B2 (en) | 1996-09-25 | 2009-06-09 | Neuralstem Biopharmaceuticals Ltd. | Stable neural stem cell line methods |
US5968829A (en) | 1997-09-05 | 1999-10-19 | Cytotherapeutics, Inc. | Human CNS neural stem cells |
DE60035191T2 (de) * | 1999-05-03 | 2008-06-19 | Neuro Therapeutics Ab | Materialien und methoden zur entwicklung von dopaminergen neuronen |
US6878543B1 (en) * | 1999-10-25 | 2005-04-12 | Nsgene Sa | Cultures of GFAP+ nestin+ cells that differentiate to neurons |
US7514259B2 (en) | 2000-02-11 | 2009-04-07 | Schepens Eye Research Institute | Isolation and transplantation of retinal stem cells |
EP1271145A1 (en) * | 2001-06-25 | 2003-01-02 | Cardion AG | Methods and cell populations for identifying and validating genomic targets, and for drug screening |
CA2461290C (en) | 2001-09-24 | 2014-11-25 | Sangamo Biosciences, Inc. | Modulation of stem cells using zinc finger proteins |
US7129034B2 (en) | 2001-10-25 | 2006-10-31 | Cedars-Sinai Medical Center | Differentiation of whole bone marrow |
US20040185429A1 (en) | 2002-12-09 | 2004-09-23 | Judith Kelleher-Andersson | Method for discovering neurogenic agents |
US8293488B2 (en) | 2002-12-09 | 2012-10-23 | Neuralstem, Inc. | Method for screening neurogenic agents |
US20050019801A1 (en) * | 2003-06-04 | 2005-01-27 | Curis, Inc. | Stem cell-based methods for identifying and characterizing agents |
IN2014CN03629A (ko) | 2004-11-17 | 2015-09-04 | Neuralstem Inc | |
EP2077092A3 (en) * | 2007-10-29 | 2009-10-21 | Taipei Veterans General Hospital | System and Methods for Screening or Analyzing Targets |
GB0815224D0 (en) * | 2008-08-20 | 2008-09-24 | Eisai London Res Lab Ltd | Screening assay |
US9540611B2 (en) | 2010-07-28 | 2017-01-10 | Neuralstem, Inc. | Methods for treating and/or reversing neurodegenerative diseases and/or disorders |
EP3492586B1 (en) | 2012-02-17 | 2024-04-17 | Schepens Eye Research Institute | Phenotype profile of human retinal progenitor cells |
CA2964927C (en) | 2014-10-20 | 2019-07-30 | Neuralstem, Inc. | Stable neural stem cells comprising an exogenous polynucleotide coding for a growth factor and methods of use thereof |
JP6844953B2 (ja) * | 2015-04-22 | 2021-03-17 | 公益財団法人東京都医学総合研究所 | アルツハイマー病研究を標的にしたグリア細胞システム |
CN105861482B (zh) * | 2016-04-05 | 2019-10-11 | 中国科学院广州生物医药与健康研究院 | 体外细胞疾病模型及其制备方法 |
EP3609511A4 (en) * | 2017-04-13 | 2020-12-23 | The Board of Trustees of the Leland Stanford Junior University | PERSONALIZED 3D NEURONAL CULTURE SYSTEM FOR GENERATING HUMAN OLIGODENDROCYTE AND STUDYING MYELINIZATION IN VITRO |
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EP0233838A3 (en) * | 1986-02-04 | 1990-01-31 | Incyte Pharmaceuticals, Inc. | Neurite-promoting factor and process for the manufacture thereof |
WO1991009936A1 (en) * | 1989-12-26 | 1991-07-11 | Hana Biologics, Inc. | 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. |
DK0669973T4 (da) * | 1992-10-28 | 2007-08-27 | Neurospheres Holdings Ltd | Biologiske faktorer og neurale stamceller |
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1995
- 1995-09-22 CA CA002200709A patent/CA2200709A1/en not_active Abandoned
- 1995-09-22 KR KR1019970701845A patent/KR970706490A/ko not_active Application Discontinuation
- 1995-09-22 PT PT95931864T patent/PT783693E/pt unknown
- 1995-09-22 DK DK01101622T patent/DK1130394T3/da active
- 1995-09-22 EP EP01101622A patent/EP1130394B1/en not_active Expired - Lifetime
- 1995-09-22 WO PCT/CA1995/000542 patent/WO1996009543A1/en active IP Right Grant
- 1995-09-22 AU AU35152/95A patent/AU714837B2/en not_active Ceased
- 1995-09-22 JP JP8510484A patent/JPH10505754A/ja active Pending
- 1995-09-22 AT AT01101622T patent/ATE345496T1/de not_active IP Right Cessation
- 1995-09-22 DE DE69535300T patent/DE69535300T2/de not_active Expired - Lifetime
- 1995-09-22 ES ES95931864T patent/ES2167461T3/es not_active Expired - Lifetime
- 1995-09-22 MX MX9702126A patent/MX9702126A/es unknown
- 1995-09-22 DE DE69523771T patent/DE69523771T2/de not_active Expired - Lifetime
- 1995-09-22 AT AT95931864T patent/ATE208495T1/de not_active IP Right Cessation
- 1995-09-22 DK DK95931864T patent/DK0783693T3/da active
- 1995-09-22 EP EP95931864A patent/EP0783693B1/en not_active Expired - Lifetime
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1997
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FI971168A0 (fi) | 1997-03-20 |
PT783693E (pt) | 2002-04-29 |
EP1130394B1 (en) | 2006-11-15 |
WO1996009543A1 (en) | 1996-03-28 |
DE69535300D1 (de) | 2006-12-28 |
ATE208495T1 (de) | 2001-11-15 |
CA2200709A1 (en) | 1996-03-28 |
AU3515295A (en) | 1996-04-09 |
MX9702126A (es) | 1997-06-28 |
FI971168A (fi) | 1997-03-20 |
AU714837B2 (en) | 2000-01-13 |
NO971245D0 (no) | 1997-03-18 |
DK1130394T3 (da) | 2007-01-08 |
DE69535300T2 (de) | 2007-06-06 |
DK0783693T3 (da) | 2002-01-14 |
EP0783693A1 (en) | 1997-07-16 |
ATE345496T1 (de) | 2006-12-15 |
NO971245L (no) | 1997-03-18 |
EP0783693B1 (en) | 2001-11-07 |
DE69523771D1 (de) | 2001-12-13 |
DE69523771T2 (de) | 2002-08-01 |
EP1130394A1 (en) | 2001-09-05 |
ES2167461T3 (es) | 2002-05-16 |
JPH10505754A (ja) | 1998-06-09 |
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