WO1999029279A2 - Survie a long terme et regeneration de neurones du systeme nerveux central - Google Patents

Survie a long terme et regeneration de neurones du systeme nerveux central Download PDF

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Publication number
WO1999029279A2
WO1999029279A2 PCT/US1998/025663 US9825663W WO9929279A2 WO 1999029279 A2 WO1999029279 A2 WO 1999029279A2 US 9825663 W US9825663 W US 9825663W WO 9929279 A2 WO9929279 A2 WO 9929279A2
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Prior art keywords
cells
survival
camp
culture
growth factor
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PCT/US1998/025663
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English (en)
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WO1999029279A3 (fr
Inventor
Barbara A. Barres
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The Board Of Trustees Of The Leland Stanford Junior University
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Application filed by The Board Of Trustees Of The Leland Stanford Junior University filed Critical The Board Of Trustees Of The Leland Stanford Junior University
Priority to AU19965/99A priority Critical patent/AU1996599A/en
Publication of WO1999029279A2 publication Critical patent/WO1999029279A2/fr
Publication of WO1999029279A3 publication Critical patent/WO1999029279A3/fr

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1825—Fibroblast growth factor [FGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1841—Transforming growth factor [TGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/204—IL-6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2093—Leukaemia inhibitory factor [LIF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-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
    • C12N2501/01—Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
    • 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
    • C12N2501/105—Insulin-like growth factors [IGF]
    • 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
    • C12N2501/13—Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins

Definitions

  • the invention includes a central nervous system neuronal cell survival factor having the following characteristics: (i) secreted by mature oligodendrocytes in a pure in vitro culture, (ii) sensitivity to heat inactivation by boiling for 5 minutes, (iii) sensitivity to inactivation by trypsin digestion, (iv) a molecular weight greater than approximately 10 kD, .and (v) application of the factor to purified cultured postnatal retinal ganglion cells increases the survival time of the cells relative to cultured cells to which the factor is not applied.
  • FIGURES Figures 1A, IB, IC, ID and IE show a schematic diagram of the panning procedure for purifying retinal ganglion cells.
  • Figures 17A and 17B show computer-generated images of P8 retinas incubated with IBMX alone (17A) or IBMX + forskolin (17B) and stained for cAMP.
  • a “defined medium” is a culture medium used for culturing a selected sample of cells, where the identities and concentrations of all of the components present in the medium are known prior to its addition to the sample of cells.
  • An exemplary defined medium is the serum-free modified Bottenstein-Sato medium (MBS; described below).
  • MBS serum-free modified Bottenstein-Sato medium
  • Serum added to a cell culture medium typically renders the resulting medium undefined, since the identity and concentration of all of the serum components is not ordinarily known.
  • the addition of "conditioned" medium to a cell culture medium renders the resulting medium undefined, since the identity and concentration of all of the components secreted by the conditioning cells into the conditioned medium are not generally known.
  • “Promoting survival” means that cells exposed to conditions that would normally result in cell death survive for a significantly longer period of time than expected, as assessed by comparison of treated cells to control, untreated cells. Such conditions include, but are not limited to lesion of presynaptic inputs, trauma, neuronal ischemia and the like.
  • glial cells can also serve to secrete certain survival factors required to prevent the neurons from undergoing apoptosis.
  • astrocytes and Schwann cells have previously been found to secrete a variety of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulin-like growth factor 1 (IGF-1), there has heretofore been no evidence to suggest that oligodendrocytes, the myelinating cells of the CNS, secrete neurotrophic factors.
  • BDNF brain-derived neurotrophic factor
  • CNTF ciliary neurotrophic factor
  • IGF-1 insulin-like growth factor 1
  • FIG. 1A-1E A retinal cell suspension (20) prepared as above and containing retinal ganglion cells (22), macrophages (24) and various other cells, including Thyl negative cells (26), was incubated with antiserum containing rabbit-anti-rat-macrophage antibodies (28; Accurate Chemical & Scientific Corp., 1:100) for 20 minutes (Fig.

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  • General Health & Medical Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biotechnology (AREA)
  • Endocrinology (AREA)
  • Genetics & Genomics (AREA)
  • Diabetes (AREA)
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  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Psychology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne une culture in vitro de cellules neuronales du système nerveux central (CNS). Cette culture est caractérisée par l'absence de cellules nourricières ou d'un milieu conditionné par des cellules nourricières, par un milieu de culture sensiblement exempt de sérum et par une viabilité améliorée. Elle concerne également des procédés servant à cultiver des cellules purifiées du système nerveux central dans des conditions déterminées pendant des périodes prolongées, ainsi que des procédés servant à favoriser la régénération et la survie de neurones détériorés du système nerveux central in vivo, et une composition pharmaceutique correspondante.
PCT/US1998/025663 1997-12-05 1998-12-03 Survie a long terme et regeneration de neurones du systeme nerveux central WO1999029279A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU19965/99A AU1996599A (en) 1997-12-05 1998-12-03 Long-term survival and regeneration of central nervous system neurons

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US98552197A 1997-12-05 1997-12-05
US08/985,521 1997-12-05

Publications (2)

Publication Number Publication Date
WO1999029279A2 true WO1999029279A2 (fr) 1999-06-17
WO1999029279A3 WO1999029279A3 (fr) 1999-10-21

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6245564B1 (en) 1997-01-23 2001-06-12 Cornell Research Foundation, Inc. Method for separating cells
US7037493B2 (en) 2000-05-01 2006-05-02 Cornell Research Foundation, Inc. Method of inducing neuronal production in the brain and spinal cord
US7150989B2 (en) 2001-08-10 2006-12-19 Cornell Research Foundation, Inc. Telomerase immortalized neural progenitor cells
WO2007048846A1 (fr) * 2005-10-27 2007-05-03 Neuraxo Biopharmaceuticals Gmbh Utilisation de composes chelateurs du fer, composes augmentant l'adenosine monophosphate cyclique ou combinaisons de ces substances pour traiter des lesions axonales dans le systeme nerveux central
WO2007073151A1 (fr) * 2005-12-21 2007-06-28 Stichting Katholieke Universiteit Équivalents de peau psoriasique
US7312025B2 (en) 2002-07-12 2007-12-25 University Of Washington Methods and systems for extended in vitro culture of neuronal cells
WO2008131368A2 (fr) 2007-04-20 2008-10-30 Acucela Inc. Composés dérivés de styrényle pour traiter des maladies et des troubles ophtalmiques
US7468277B2 (en) 1999-12-23 2008-12-23 Cornell Research Foundation, Inc. Enriched preparation of human fetal multipotential neural stem cells
WO2009005794A2 (fr) 2007-06-29 2009-01-08 Acucela, Inc. Dérivés d'alcynylphényle pour traiter les maladies et les affections ophtalmiques
WO2009045479A1 (fr) 2007-10-05 2009-04-09 Acucela Inc. Composés d'alcoxy pour le traitement de maladies
US7576065B2 (en) 2002-02-15 2009-08-18 Cornell Research Foundation, Inc. Enhancing neurotrophin-induced neurogenesis by endogenous neural progenitor cells by concurrent overexpression of brain derived neurotrophic factor and an inhibitor of a pro-gliogenic bone morphogenetic protein
US8263402B1 (en) 1998-10-19 2012-09-11 Cornell Research Foundation, Inc. Method for isolating and purifying oligodendrocytes and oligodendrocyte progenitor cells
US9133154B2 (en) 2013-03-12 2015-09-15 Acucela Inc. Substituted 3-phenylpropylamine derivatives for the treatment of ophthalmic diseases and disorders
US9447078B2 (en) 2012-01-20 2016-09-20 Acucela Inc. Substituted heterocyclic compounds for disease treatment
CN115404219A (zh) * 2022-09-09 2022-11-29 中国医学科学院医学生物学研究所 一种树鼩视网膜神经节细胞的分离培养方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5584885A (en) * 1994-04-28 1996-12-17 Seckel; Brooke R. Nerve regeneration chamber
US5667968A (en) * 1989-08-30 1997-09-16 Regeneron Pharmaceuticals, Inc. Prevention of retinal injury and degeneration by specific factors

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5667968A (en) * 1989-08-30 1997-09-16 Regeneron Pharmaceuticals, Inc. Prevention of retinal injury and degeneration by specific factors
US5584885A (en) * 1994-04-28 1996-12-17 Seckel; Brooke R. Nerve regeneration chamber

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RYDEL et al., "cAMP Analogs Promote Survival and Neurite Outgrowth in Cultures of Rat Sympathetic and Sensory Neurons Independently of Nerve Growth Factor", PROC. NATL. ACAD. SCI. USA, February 1988, Vol. 85, pages 1257-1261, XP002919694 *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6692957B2 (en) 1997-01-23 2004-02-17 Cornell Research Foundation, Inc. Method for separating cells
US6245564B1 (en) 1997-01-23 2001-06-12 Cornell Research Foundation, Inc. Method for separating cells
US8263402B1 (en) 1998-10-19 2012-09-11 Cornell Research Foundation, Inc. Method for isolating and purifying oligodendrocytes and oligodendrocyte progenitor cells
US7468277B2 (en) 1999-12-23 2008-12-23 Cornell Research Foundation, Inc. Enriched preparation of human fetal multipotential neural stem cells
US7037493B2 (en) 2000-05-01 2006-05-02 Cornell Research Foundation, Inc. Method of inducing neuronal production in the brain and spinal cord
US7807145B2 (en) 2000-05-01 2010-10-05 Cornell Research Foundation, Inc. Method of inducing neuronal production in the brain and spinal cord
US7803752B2 (en) 2000-05-01 2010-09-28 Cornell Research Foundation, Inc. Method of inducing neuronal production in the caudate nucleus and putamen
US7150989B2 (en) 2001-08-10 2006-12-19 Cornell Research Foundation, Inc. Telomerase immortalized neural progenitor cells
US7576065B2 (en) 2002-02-15 2009-08-18 Cornell Research Foundation, Inc. Enhancing neurotrophin-induced neurogenesis by endogenous neural progenitor cells by concurrent overexpression of brain derived neurotrophic factor and an inhibitor of a pro-gliogenic bone morphogenetic protein
US7312025B2 (en) 2002-07-12 2007-12-25 University Of Washington Methods and systems for extended in vitro culture of neuronal cells
WO2007048846A1 (fr) * 2005-10-27 2007-05-03 Neuraxo Biopharmaceuticals Gmbh Utilisation de composes chelateurs du fer, composes augmentant l'adenosine monophosphate cyclique ou combinaisons de ces substances pour traiter des lesions axonales dans le systeme nerveux central
WO2007073151A1 (fr) * 2005-12-21 2007-06-28 Stichting Katholieke Universiteit Équivalents de peau psoriasique
US8653142B2 (en) 2007-04-20 2014-02-18 Acucela Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders
WO2008131368A2 (fr) 2007-04-20 2008-10-30 Acucela Inc. Composés dérivés de styrényle pour traiter des maladies et des troubles ophtalmiques
US8420863B2 (en) 2007-04-20 2013-04-16 Acucela, Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders
US9314467B2 (en) 2007-04-20 2016-04-19 Acucela Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders
US9421210B2 (en) 2007-04-20 2016-08-23 Acucela Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders
US10201545B2 (en) 2007-04-20 2019-02-12 Acucela Inc. Styrenyl derivative compounds for treating ophthalmic diseases and disorders
WO2009005794A2 (fr) 2007-06-29 2009-01-08 Acucela, Inc. Dérivés d'alcynylphényle pour traiter les maladies et les affections ophtalmiques
WO2009045479A1 (fr) 2007-10-05 2009-04-09 Acucela Inc. Composés d'alcoxy pour le traitement de maladies
EP3210966A1 (fr) 2007-10-05 2017-08-30 Acucela, Inc. Alcoxyphénylpropylamines pour le traitement de la dégénérescence maculaire liée à l'âge
US9447078B2 (en) 2012-01-20 2016-09-20 Acucela Inc. Substituted heterocyclic compounds for disease treatment
US9133154B2 (en) 2013-03-12 2015-09-15 Acucela Inc. Substituted 3-phenylpropylamine derivatives for the treatment of ophthalmic diseases and disorders
CN115404219A (zh) * 2022-09-09 2022-11-29 中国医学科学院医学生物学研究所 一种树鼩视网膜神经节细胞的分离培养方法
CN115404219B (zh) * 2022-09-09 2023-10-27 中国医学科学院医学生物学研究所 一种树鼩视网膜神经节细胞的分离培养方法

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Publication number Publication date
AU1996599A (en) 1999-06-28
WO1999029279A3 (fr) 1999-10-21

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