WO2001083715A8 - Derivation of midbrain dopaminergic neurons from embryonic stem cells - Google Patents

Derivation of midbrain dopaminergic neurons from embryonic stem cells

Info

Publication number
WO2001083715A8
WO2001083715A8 PCT/US2001/014051 US0114051W WO0183715A8 WO 2001083715 A8 WO2001083715 A8 WO 2001083715A8 US 0114051 W US0114051 W US 0114051W WO 0183715 A8 WO0183715 A8 WO 0183715A8
Authority
WO
WIPO (PCT)
Prior art keywords
cells
cns
differentiated
expansion
cns precursor
Prior art date
Application number
PCT/US2001/014051
Other languages
French (fr)
Other versions
WO2001083715A2 (en
WO2001083715A3 (en
Inventor
Sang-Hun Lee
Nadya Lumelsky
Lorenz Studer
Ron D G Mckay
Jonathan Auerbach
Jong-Hoon Kim
Original Assignee
Us Gov Health & Human Serv
Sang-Hun Lee
Nadya Lumelsky
Lorenz Studer
Ron D G Mckay
Jonathan Auerbach
Jong-Hoon Kim
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Us Gov Health & Human Serv, Sang-Hun Lee, Nadya Lumelsky, Lorenz Studer, Ron D G Mckay, Jonathan Auerbach, Jong-Hoon Kim filed Critical Us Gov Health & Human Serv
Priority to US10/258,975 priority Critical patent/US20030211605A1/en
Priority to AU2001259323A priority patent/AU2001259323A1/en
Publication of WO2001083715A2 publication Critical patent/WO2001083715A2/en
Publication of WO2001083715A3 publication Critical patent/WO2001083715A3/en
Publication of WO2001083715A8 publication Critical patent/WO2001083715A8/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0619—Neurons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/119—Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/40—Regulators of development
    • C12N2501/41—Hedgehog proteins; Cyclopamine (inhibitor)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Neurosurgery (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention provides a method of culturing cells. The method generally includes five stages: (1) expansion of ES cells; (2) generation of embryoid bodies; (3) selection of CNS precursor cells; (4) expansion of CNS precursor cells; and (5) differentiation of CNS precursor cells. During the expansion phase, the CNS precursor cells are cultured in a media which includes at least one neurologic agent such as bFGF, SHH, and FGF8. The expanded CNS precursors are differentiated by withdrawal of at least one neurologic agent, typically, bFGF. Preferably, the differentiation media includes ascorbic acid. The method of the invention can be used to culture a variety of cells, preferably neuronal cells, including, but not limited to dopaminergic neuron cells, cholinergic neuronal cells and serotonergic neuron cells. The invention also provides a method for treating a neurological disorder, such as Parkinson's disease, a method of introducing a gene product into a brain of a patient, and an assay for neurologically active substances. The invention further provides a cell culture which includes differentiated neuron cells, of which at least about 20 % of the differentiated neurons are dopaminergic neurons.
PCT/US2001/014051 2000-05-01 2001-05-01 Derivation of midbrain dopaminergic neurons from embryonic stem cells WO2001083715A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/258,975 US20030211605A1 (en) 2001-05-01 2001-05-01 Derivation of midbrain dopaminergic neurons from embryonic stem cells
AU2001259323A AU2001259323A1 (en) 2000-05-01 2001-05-01 Derivation of midbrain dopaminergic neurons from embryonic stem cells

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US20100500P 2000-05-01 2000-05-01
US60/201,005 2000-05-01

Publications (3)

Publication Number Publication Date
WO2001083715A2 WO2001083715A2 (en) 2001-11-08
WO2001083715A3 WO2001083715A3 (en) 2002-05-23
WO2001083715A8 true WO2001083715A8 (en) 2002-12-27

Family

ID=22744085

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/014051 WO2001083715A2 (en) 2000-05-01 2001-05-01 Derivation of midbrain dopaminergic neurons from embryonic stem cells

Country Status (2)

Country Link
AU (1) AU2001259323A1 (en)
WO (1) WO2001083715A2 (en)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6667176B1 (en) 2000-01-11 2003-12-23 Geron Corporation cDNA libraries reflecting gene expression during growth and differentiation of human pluripotent stem cells
US20050042749A1 (en) 2001-05-16 2005-02-24 Carpenter Melissa K. Dopaminergic neurons and proliferation-competent precursor cells for treating Parkinson's disease
ES2292564T3 (en) 2000-02-11 2008-03-16 Philadelphia Health And Education Corporation DIFFERENTIATION OF CELLS OF THE OSEA MEDULA IN NEURON CELLS AND ASSOCIATED USES.
US7250294B2 (en) 2000-05-17 2007-07-31 Geron Corporation Screening small molecule drugs using neural cells differentiated from human embryonic stem cells
GB2379447B (en) 2000-05-17 2004-12-29 Geron Corp Neural progenitor cell populations
US7588937B2 (en) 2001-10-03 2009-09-15 Wisconsin Alumni Research Foundation Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells
US8153424B2 (en) 2001-10-03 2012-04-10 Wisconsin Alumni Research Foundation Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells
US6887706B2 (en) 2001-10-03 2005-05-03 Wisconsin Alumni Research Foundation Method of in vitro differentiation of transplantable neural precursor cells from primate embryonic stem cells
WO2003055992A2 (en) * 2001-12-28 2003-07-10 Cellartis Ab A method for the establishment of a pluripotent human blastocyst-derived stem cell line
US20050129664A1 (en) * 2002-01-09 2005-06-16 Hideyuki Okano Remedy for dysmnesia
US20030162290A1 (en) * 2002-01-25 2003-08-28 Kazutomo Inoue Method for inducing differentiation of embryonic stem cells into functioning cells
WO2003104444A1 (en) 2002-06-05 2003-12-18 Es Cell International Pte Ltd Generation of neural stem cells from undifferentiated human embryonic stem cells
EP1534068A4 (en) * 2002-08-08 2006-08-23 Univ Georgia Res Found Compositions and methods for neural differentiation of embryonic stem cells
AU2004219851B2 (en) 2003-03-12 2009-12-17 Reliance Life Sciences Pvt. Ltd. Derivation of terminally differentiated dopaminergic neurons from human embryonic stem cells
US7638328B2 (en) 2003-05-08 2009-12-29 Cellartis Ab Method for efficient transfer of human blastocyst-derived stem cells (hBS cells) from a feeder-supported to a feeder-free culture system, long-term propagation of hBS cells under feeder-free conditions and use of cultured hBS cells for applications in myocardial regeneration
WO2004099395A2 (en) * 2003-05-08 2004-11-18 Cellartis Ab A method for the generation of neural progenitor cells
WO2005017131A2 (en) * 2003-08-14 2005-02-24 THE GOUVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT F HEALTH AND HUMAN SERVICES Methods for the differentiation of human stem cells
CA2536588C (en) * 2003-08-29 2018-04-24 Wisconsin Alumni Research Foundation Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells
US7820439B2 (en) 2003-09-03 2010-10-26 Reliance Life Sciences Pvt Ltd. In vitro generation of GABAergic neurons from pluripotent stem cells
US20080199437A1 (en) * 2004-07-22 2008-08-21 Eisai Co., Ltd. Lrp4/Corin Dopaminergic Neuron Progenitor Cell Markers
DE102004062376A1 (en) 2004-12-14 2006-06-22 Newfrey Llc, Newark Method and power supply for generating an electric arc current and system for short-time arc stud welding
GB0623635D0 (en) * 2006-11-27 2007-01-03 Stem Cell Sciences Uk Ltd Pluripotent cell growth media
US9750768B2 (en) 2011-05-20 2017-09-05 The Mclean Hospital Corporation Methods for purifying midbrain dopaminergic neural progenitor cells
JP6090937B2 (en) 2011-07-27 2017-03-08 国立大学法人京都大学 Novel dopaminergic neural progenitor cell marker

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991009936A1 (en) * 1989-12-26 1991-07-11 Hana Biologics, Inc. Proliferated neuron progenitor cell product and process
DE19756864C5 (en) * 1997-12-19 2014-07-10 Oliver Brüstle Neural precursor cells, methods for their production and their use for the therapy of neural defects
JP3291698B2 (en) * 1998-07-24 2002-06-10 スティーブン・カーティン Variable eyeglass lens

Also Published As

Publication number Publication date
WO2001083715A2 (en) 2001-11-08
AU2001259323A1 (en) 2001-11-12
WO2001083715A3 (en) 2002-05-23

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