WO1999064565A3 - Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells - Google Patents

Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells Download PDF

Info

Publication number
WO1999064565A3
WO1999064565A3 PCT/US1999/012847 US9912847W WO9964565A3 WO 1999064565 A3 WO1999064565 A3 WO 1999064565A3 US 9912847 W US9912847 W US 9912847W WO 9964565 A3 WO9964565 A3 WO 9964565A3
Authority
WO
WIPO (PCT)
Prior art keywords
stem cells
hematopoietic stem
mesenchymal stem
regulation
human mesenchymal
Prior art date
Application number
PCT/US1999/012847
Other languages
French (fr)
Other versions
WO1999064565A9 (en
WO1999064565A2 (en
Inventor
Mark A Thiede
Gabriel Mbalaviele
Original Assignee
Osiris Therapeutics Inc
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 Osiris Therapeutics Inc filed Critical Osiris Therapeutics Inc
Priority to JP2000553555A priority Critical patent/JP2003505006A/en
Priority to DE69937347T priority patent/DE69937347T2/en
Priority to CA002330190A priority patent/CA2330190C/en
Priority to EP99955496A priority patent/EP1084230B1/en
Priority to DK99955496T priority patent/DK1084230T3/en
Priority to AU43364/99A priority patent/AU4336499A/en
Publication of WO1999064565A2 publication Critical patent/WO1999064565A2/en
Publication of WO1999064565A3 publication Critical patent/WO1999064565A3/en
Publication of WO1999064565A9 publication Critical patent/WO1999064565A9/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
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0643—Osteoclasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • 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
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/38—Vitamins
    • 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
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/42—Organic phosphate, e.g. beta glycerophosphate
    • 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
    • C12N2501/30—Hormones
    • C12N2501/38—Hormones with nuclear receptors
    • C12N2501/39—Steroid hormones
    • 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
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1352—Mesenchymal stem cells
    • C12N2502/1358—Bone marrow mesenchymal stem cells (BM-MSC)
    • 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
    • C12N2503/00—Use of cells in diagnostics
    • C12N2503/02—Drug screening
    • 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
    • C12N2510/00—Genetically modified cells
    • 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
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/10—Mineral substrates
    • C12N2533/18—Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells

Abstract

The invention relates to the induction of hematopoietic stem cells to differentiate into osteoclasts by culturing hematopoietic stem cells with human mesenchymal stem cells, and, in a preferred embodiment, using no exogenous cytokines. Differentiation of the mesenchymal stem cells into osteoblasts inhibited the differentiation of hematopoietic stem cells into osteoclasts. In addition, hematopoietic stem cells can be genetically engineered to carry genes of interest particularly for the expression of physiologically active proteins. In the presence of mesenchymal stem cells, the transduced cells carry the new genetic material and express gene products that can be used to modulate bone resorption.
PCT/US1999/012847 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells WO1999064565A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2000553555A JP2003505006A (en) 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation by using human mesenchymal stem cells
DE69937347T DE69937347T2 (en) 1998-06-08 1999-06-08 REGULATION OF HEMATOPOIETIC STEM CELL DIFFERENTIATION THROUGH THE USE OF HUMAN MESENCHYMAL STEM CELLS
CA002330190A CA2330190C (en) 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells
EP99955496A EP1084230B1 (en) 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells
DK99955496T DK1084230T3 (en) 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation using human mesenchymal stem cells
AU43364/99A AU4336499A (en) 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US8843198P 1998-06-08 1998-06-08
US60/088,431 1998-06-08
US9923398P 1998-09-04 1998-09-04
US60/099,233 1998-09-04

Publications (3)

Publication Number Publication Date
WO1999064565A2 WO1999064565A2 (en) 1999-12-16
WO1999064565A3 true WO1999064565A3 (en) 2000-02-24
WO1999064565A9 WO1999064565A9 (en) 2000-04-13

Family

ID=26778653

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/012847 WO1999064565A2 (en) 1998-06-08 1999-06-08 Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells

Country Status (12)

Country Link
US (1) US6255112B1 (en)
EP (1) EP1084230B1 (en)
JP (1) JP2003505006A (en)
AT (1) ATE375799T1 (en)
AU (1) AU4336499A (en)
CA (2) CA2330190C (en)
CY (1) CY1107121T1 (en)
DE (1) DE69937347T2 (en)
DK (1) DK1084230T3 (en)
ES (1) ES2296413T3 (en)
PT (1) PT1084230E (en)
WO (1) WO1999064565A2 (en)

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1218487A2 (en) * 1999-09-23 2002-07-03 Cell Science Therapeutics Methods and devices for obtaining non-hematopoietic lineage cells from hematopoietic progenitor cells
AU2002239424A1 (en) * 2000-11-14 2002-05-27 The University Of Louisville Research Foundation, Inc. Methods for enhancing engraftment of purified hematopoietic stem cells in allogeneic recipients
AU2002220209B2 (en) 2000-12-06 2006-05-25 Robert J. Hariri Method of collecting placental stem cells
US20030032179A1 (en) 2000-12-06 2003-02-13 Hariri Robert J. Post-partum mammalian placenta, its use and placental stem cells therefrom
US7311905B2 (en) 2002-02-13 2007-12-25 Anthrogenesis Corporation Embryonic-like stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells
KR101012952B1 (en) * 2001-02-14 2011-02-08 안트로제네시스 코포레이션 Post-partum mammalian placenta, its use and placental stem cells therefrom
AU2002331008A1 (en) * 2001-08-08 2003-02-24 Schering Corporation Uses of mammalian cytokine; related reagents
EP1487463A2 (en) * 2002-03-02 2004-12-22 Board Of Regents The University Of Texas System Local production and/or delivery of anti-cancer agents by stromal cell precursors
US7498171B2 (en) * 2002-04-12 2009-03-03 Anthrogenesis Corporation Modulation of stem and progenitor cell differentiation, assays, and uses thereof
JP2005528105A (en) * 2002-05-30 2005-09-22 セルジーン・コーポレーション Methods of using JNK or MKK inhibitors to modulate cell differentiation and to treat myeloproliferative diseases and myelodysplastic syndromes
US20040028661A1 (en) * 2002-08-07 2004-02-12 Bartelmez Stephen H. Expansion of cells using thrombopoietin and anti-transforming growth factor-beta
KR101042448B1 (en) 2002-11-26 2011-06-16 안트로제네시스 코포레이션 Cytotherapeutics, cytotherapeutic units and methods for treatments using them
ATE482725T1 (en) * 2003-04-01 2010-10-15 Us Dept Of Veteran S Affaires STEM CELL, PROGRESSOR CELL OR TARGET CELL BASED TREATMENT OF MULTI-ORGAN FAILURE.
US20040209246A1 (en) * 2003-04-15 2004-10-21 Agouron Pharmaceuticals, Inc. Dual reporter/dye reduction methodology for evaluating antiviral and cytotoxicity of hepatitis C virus inhibitors
EP1479760A1 (en) * 2003-05-19 2004-11-24 ProBioGen AG Artificial immune organ
WO2005035742A2 (en) 2003-10-08 2005-04-21 Vet-Stem Inc. Methods of preparing and using stem cell compositions and kits comprising the same
US20050112551A1 (en) * 2003-11-24 2005-05-26 Agouron Pharmaceuticals, Inc. Dual assay for evaluating activity and cytotoxicity of compounds in the same population of cells
WO2006030442A2 (en) * 2004-09-16 2006-03-23 Gamida-Cell Ltd. Methods of ex vivo progenitor and stem cell expansion by co-culture with mesenchymal cells
CA2512667A1 (en) * 2005-01-07 2006-07-07 Takahiro Ochiya Human hepatocyte-like cells and uses thereof
EP1880002A4 (en) * 2005-05-10 2009-03-11 Us Health Therapy of kidney diseases and multiorgan failure with mesenchymal stem cells and mesenchymal stem cell conditioned media
ES2452595T3 (en) 2005-10-13 2014-04-02 Anthrogenesis Corporation Immunomodulation using placental stem cells
US8846393B2 (en) * 2005-11-29 2014-09-30 Gamida-Cell Ltd. Methods of improving stem cell homing and engraftment
AU2006332679A1 (en) 2005-12-29 2007-07-12 Anthrogenesis Corporation Co-culture of placental stem cells and stem cells from a second source
KR20210122908A (en) 2005-12-29 2021-10-12 안트로제네시스 코포레이션 Placental stem cell populations
CN101501185A (en) * 2006-06-09 2009-08-05 人类起源公司 Placental niche and use thereof to culture stem cells
US7993918B2 (en) * 2006-08-04 2011-08-09 Anthrogenesis Corporation Tumor suppression using placental stem cells
KR100818213B1 (en) 2006-09-22 2008-04-01 재단법인서울대학교산학협력재단 Human Cord Blood Multipotent Stem Cell Having Enhanced Proliferation Ability With Osteoclast-based Niche-like Structure and Method for Preparing the Same
US20080118477A1 (en) * 2006-11-09 2008-05-22 Rush University Medical Center Umbilical cord mesenchymal stem cells support cord blood hematopoiesis
DK2120977T3 (en) 2007-02-12 2013-08-12 Anthrogenesis Corp Treatment of inflammatory diseases using placental stem cells
EP2129775A1 (en) 2007-02-12 2009-12-09 Anthrogenesis Corporation Hepatocytes and chondrocytes from adherent placental stem cells; and cd34+, cd45- placental stem cell-enriched cell populations
US9200253B1 (en) 2007-08-06 2015-12-01 Anthrogenesis Corporation Method of producing erythrocytes
CN101173247B (en) * 2007-08-08 2010-06-02 中国人民解放军军事医学科学院基础医学研究所 Method for culturing osteoclast with mesenchyma stem cell combined with cell factor
KR20210022148A (en) 2007-09-28 2021-03-02 안트로제네시스 코포레이션 Tumor suppression using human placental perfusate and human placenta-derived intermediate natural killer cells
KR20110050521A (en) 2008-08-20 2011-05-13 안트로제네시스 코포레이션 Improved cell composition and methods of making the same
KR101903049B1 (en) 2008-08-20 2018-11-07 안트로제네시스 코포레이션 Treatment of stroke using isolated placental cells
KR20110050688A (en) 2008-08-22 2011-05-16 안트로제네시스 코포레이션 Methods and compositions for treatment of bone defects with placental cell populations
AU2009316541B2 (en) 2008-11-19 2015-08-06 Celularity Inc. Amnion derived adherent cells
CA2767014C (en) 2009-07-02 2022-01-25 Anthrogenesis Corporation Method of producing erythrocytes without feeder cells
US20120177618A1 (en) * 2009-07-14 2012-07-12 Massachusetts Institute Of Technology Hematopoietic stromal progenitor cells and uses thereof
US9005967B2 (en) 2010-01-22 2015-04-14 Kyoto University Myc variants improve induced pluripotent stem cell generation efficiency
EP3284818B1 (en) 2010-01-26 2022-03-09 Celularity Inc. Treatment of bone-related cancers using placental stem cells
KR20230054905A (en) 2010-04-07 2023-04-25 셀룰래리티 인코포레이티드 Angiogenesis using placental stem cells
WO2011127113A1 (en) 2010-04-08 2011-10-13 Anthrogenesis Corporation Treatment of sarcoidosis using placental stem cells
ES2666746T3 (en) 2010-07-13 2018-05-07 Anthrogenesis Corporation Methods to generate natural cytolytic lymphocytes
US9725689B2 (en) 2010-10-08 2017-08-08 Terumo Bct, Inc. Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system
JP6029137B2 (en) 2010-12-03 2016-11-24 国立大学法人京都大学 Efficient method for establishing induced pluripotent stem cells
US8969315B2 (en) 2010-12-31 2015-03-03 Anthrogenesis Corporation Enhancement of placental stem cell potency using modulatory RNA molecules
PL2714059T3 (en) 2011-06-01 2019-04-30 Celularity Inc Treatment of pain using placental stem cells
WO2013055476A1 (en) 2011-09-09 2013-04-18 Anthrogenesis Corporation Treatment of amyotrophic lateral sclerosis using placental stem cells
WO2013121426A1 (en) 2012-02-13 2013-08-22 Gamida-Cell Ltd. Culturing of mesenchymal stem cells
US9175266B2 (en) 2012-07-23 2015-11-03 Gamida Cell Ltd. Enhancement of natural killer (NK) cell proliferation and activity
US9567569B2 (en) 2012-07-23 2017-02-14 Gamida Cell Ltd. Methods of culturing and expanding mesenchymal stem cells
US9763983B2 (en) 2013-02-05 2017-09-19 Anthrogenesis Corporation Natural killer cells from placenta
EP3569699A1 (en) 2013-09-04 2019-11-20 Otsuka Pharmaceutical Factory, Inc. Method for preparing pluripotent stem cells
WO2015073913A1 (en) 2013-11-16 2015-05-21 Terumo Bct, Inc. Expanding cells in a bioreactor
WO2015148704A1 (en) 2014-03-25 2015-10-01 Terumo Bct, Inc. Passive replacement of media
CN106715676A (en) 2014-09-26 2017-05-24 泰尔茂比司特公司 Scheduled feed
KR101566450B1 (en) * 2015-04-03 2015-11-05 (유)스템메디케어 A Method for mass production of proteins from mesenchymal stem cells
WO2017004592A1 (en) 2015-07-02 2017-01-05 Terumo Bct, Inc. Cell growth with mechanical stimuli
US11685883B2 (en) 2016-06-07 2023-06-27 Terumo Bct, Inc. Methods and systems for coating a cell growth surface
US11104874B2 (en) 2016-06-07 2021-08-31 Terumo Bct, Inc. Coating a bioreactor
US11624046B2 (en) 2017-03-31 2023-04-11 Terumo Bct, Inc. Cell expansion
US11702634B2 (en) 2017-03-31 2023-07-18 Terumo Bct, Inc. Expanding cells in a bioreactor

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995002040A2 (en) * 1993-07-07 1995-01-19 GSF - Forschungszentrum für Umwelt und Gesundheit GmbH New stromal cell lines from human bone marrow and their use
US5486359A (en) * 1990-11-16 1996-01-23 Osiris Therapeutics, Inc. Human mesenchymal stem cells
WO1996032469A1 (en) * 1995-04-10 1996-10-17 Merck & Co., Inc. Method for producing a highly enriched population of osteoclast cells
US5670351A (en) * 1989-06-15 1997-09-23 The Regents Of The University Of Michigan Methods and compositions for the ex vivo replication of human hematopoietic stem cells

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5670351A (en) * 1989-06-15 1997-09-23 The Regents Of The University Of Michigan Methods and compositions for the ex vivo replication of human hematopoietic stem cells
US5486359A (en) * 1990-11-16 1996-01-23 Osiris Therapeutics, Inc. Human mesenchymal stem cells
WO1995002040A2 (en) * 1993-07-07 1995-01-19 GSF - Forschungszentrum für Umwelt und Gesundheit GmbH New stromal cell lines from human bone marrow and their use
WO1996032469A1 (en) * 1995-04-10 1996-10-17 Merck & Co., Inc. Method for producing a highly enriched population of osteoclast cells

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MBALAVIELE G ET AL: "Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors.", ENDOCRINOLOGY, (1999 AUG) 140 (8) 3736-43., XP000857472 *
TAKAHASHI S ET AL: "Development and characterization of a human marrow stromal cell line that enhances osteoclast -like cell formation.", ENDOCRINOLOGY, (1995 APR) 136 (4) 1441-9., XP000857459 *

Also Published As

Publication number Publication date
ATE375799T1 (en) 2007-11-15
US6255112B1 (en) 2001-07-03
DK1084230T3 (en) 2008-03-03
WO1999064565A9 (en) 2000-04-13
DE69937347D1 (en) 2007-11-29
DE69937347T2 (en) 2008-09-04
JP2003505006A (en) 2003-02-12
WO1999064565A2 (en) 1999-12-16
ES2296413T3 (en) 2008-04-16
CA2330190A1 (en) 1999-12-16
CA2330190C (en) 2009-12-22
AU4336499A (en) 1999-12-30
PT1084230E (en) 2008-01-25
CA2680649A1 (en) 1999-12-16
CY1107121T1 (en) 2012-10-24
EP1084230B1 (en) 2007-10-17
EP1084230A2 (en) 2001-03-21

Similar Documents

Publication Publication Date Title
WO1999064565A3 (en) Regulation of hematopoietic stem cell differentiation by the use of human mesenchymal stem cells
WO2000006705A3 (en) Genetically modified cd34-negative adherently growing stem cells and their use in gene therapy
KR100339316B1 (en)
WO2003014313A3 (en) Alternative compositions and methods for the culture of stem cells
EP0953354A4 (en) Hematopoietic stem cell proliferating agents
AU2126688A (en) Serum free media for the growth of insect cells and expression of products thereby
MY140230A (en) Activating expression of an amplifying endogenous gene by homologous recombination
EP1712616A4 (en) Induction of myocardial cell with the use of mammalian bone marrow cell or cord blood-origin cell and fat tissue
JP2003505006A5 (en)
AU4266597A (en) Use of a non-mammalian dna virus to express an exogenous gene in a mammalian cell
AU3808895A (en) Active retinoic acid free culture medium for avian totipotential embryonic cells
WO1999046366A8 (en) Uses for humane non-autologous mesenchymal stem cells
WO2001051616A3 (en) Techniques for growth and differentiation of human pluripotent stem cells
AU3675095A (en) Use of a non-mammalian dna virus to express an exogenous gene in a mammalian cell
IL164817A (en) Composition comprising near diploid immortalized keratinocytes cells
EP1616960A3 (en) Human pancreatic cell lines: developments and uses
WO2003025151A3 (en) Circadian control of stem/progenitor cell self-renewal and differentiation and of clock controlled gene expression
WO1999035245A3 (en) Methods for preparing and using immortalized human neuroendocrine cells
ATE243741T1 (en) SUPPLY OF GENETIC PRODUCTS USING MESANGIUM CELLS
IL148360A0 (en) A herpes viral mutant and pharmaceutical compositions containing the same
AU2704197A (en) Immortalized retinal cell lines and their applications
EP0550769A4 (en)
EP0808364A4 (en) Human pancreatic cell lines: developments and uses
WO1996009399A3 (en) Chimeric adenovirus for gene delivery
WO2002044355A3 (en) Protozoan expression systems for lysosomal storage disease genes

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

AK Designated states

Kind code of ref document: C2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: C2

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1999955496

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2330190

Country of ref document: CA

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 553555

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 1999955496

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 1999955496

Country of ref document: EP