+

WO1999043785A1 - Derivation de cellules et de tissus a partir du stade cellulaire pre-souche pour les therapies de transplantation - Google Patents

Derivation de cellules et de tissus a partir du stade cellulaire pre-souche pour les therapies de transplantation Download PDF

Info

Publication number
WO1999043785A1
WO1999043785A1 PCT/US1999/004188 US9904188W WO9943785A1 WO 1999043785 A1 WO1999043785 A1 WO 1999043785A1 US 9904188 W US9904188 W US 9904188W WO 9943785 A1 WO9943785 A1 WO 9943785A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
stem cells
embryonic stem
line
embryonic
Prior art date
Application number
PCT/US1999/004188
Other languages
English (en)
Inventor
Gary D. Hodgen
Original Assignee
Medical College Of Hampton Roads
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 Medical College Of Hampton Roads filed Critical Medical College Of Hampton Roads
Priority to CA002320423A priority Critical patent/CA2320423A1/fr
Priority to AU28799/99A priority patent/AU757036B2/en
Priority to JP2000533525A priority patent/JP2002504362A/ja
Priority to EP99909633A priority patent/EP1056835A4/fr
Publication of WO1999043785A1 publication Critical patent/WO1999043785A1/fr

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
    • C12N5/0603—Embryonic cells ; Embryoid bodies
    • C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to the derivation of cells and tissues from embryonic pre-stem cells for transplantation therapies .
  • This invention relates to the use of dispersed morula cells in preference to inner cell mass (ICM) from blastocysts.
  • the morula stage is the last pre-embryonic
  • pre-stem cells embryonic stem cells
  • the ICM from the blastocyst is already differentiated from trophoblastic cells, which are by then destined to become part of the placenta.
  • This invention also relates to the use of chimeric introductions into pre-stem cell cultures and stem cell propagations in culture. That is, "teacher-cells” or spent media from them, that derived from other sources (e.g. adults, cord blood, fetal tissues, etc.) will "teach" undifferentiated pre-stem cells how to convert to our sought-after therapeutic cell population both more rapidly and more preferentially.
  • This invention also relates to the identification and use of certain early markers of stem cell
  • the present invention provides for a method of isolating and propagating a line of embryonic stem cells that originates from either morulae (pre-stem) or blastocyst (ICM stem cells) . Therefore, Morula stage, undifferentiated pre-stem cells will be used as progenitors of stem cell populations. The propagated line of embryonic stem cells are then used for the purpose of transplanting cells, tissues or organs.
  • the propagation of stem cells can be initiated by formation of chimeric inner cell mass cells.
  • Chimeric ICMs will be developed from blastocysts. From such ICMs, superior stem cell cultures are derived.
  • the formation of chimeric inner cell mass cells comprises nuclear transplantation, mitochondrial substitution, or cytoplasmic depletion.
  • At least one regulatory factor is used to propagate the line of embryonic stem cells. More preferably, the regulatory factor is derived from "Teacher cells” or “Teacher cells'” spent culture medium. "Teacher cells” will be introduced into less differentiated pre-stem or early stage stem cells to accelerate propagation of target stem cells. Alternatively, spent media from
  • teacher cells can be used to accelerate the propagation of the target stem cells.
  • the embryonic stem cells are cultured in a medium in the presence of at least one agent or cytokine in order to differentiate into target specific cells or tissues.
  • the agent or cytokine is selected from the group consisting of IL-1, TNF- ⁇ , IL-6, PTH, PDGF, PGE ⁇ cAMP, estrogens, anti- estrogens, progestins, anti-progestins, cortisol, GH, androgens, I 3 /T 3 , VGEF and cyclosporin.
  • the concentration of the agent or cytokine in culture medium is from about 1.0 pg/ml to about 10.0 ng/ml.
  • the target specific cells are selected from the group consisting of nerve cells, bone cells, immune cells, and pancreatic beta cells.
  • Some such markers are, for example: Fe++ sequestration, Hg accumulation, myeloid fibers, nerve growth factor, apoptotic factors, insulin synthesis, dopamine loading, hemoglobin loading, etc. Additionally, other early markers of embryonic stem cells can be identified.
  • embryonic stem (ES) cells are derived from either morula or blastocyst stage embryos by placing cells on fibroblast feeder layers. The colonies are evaluated for differentiation state using accepted markers. Further - 4 -
  • Clonal properties of the propagated stem cells can be achieved by adding apoptotic factors, cytokines or other agents to the culture medium to eliminate contaminating members of the stem cells that did not properly differentiate.
  • the cytokines or agents are selected from the group consisting of IL-1, TNF- , I -6, PTH, PDGF, PGE 2 , cAMP, estrogens, anti-estrogens, progestins, anti-progestins, cortisol, GH, androgens, I 3 /T 3 , VGEF and cyclosporin.
  • the propagation of the line of embryonic stem cells is done in vivo by transplanting "Teacher cells" into an area sufficiently close to the embryonic stem cells to allow for at least one regulatory factor made by the teacher cells to contact the embryonic cells.
  • the presence or absence of different concentrations of calcium can be used to regulate the propagation of the line of embryonic stem cells.
  • the propagated line of embryonic stem cells is grown in a three dimensional manner before being used for transplantation.
  • This invention will allow for the efficient, safe and commercially viable derivation of cells and tissues - 5 -
  • embryonic pre-stem cells for transplantation therapies. Specifically, growing-out of human blastocysts at a rate greater than 50% from the 2-cell stage of the pre-embryo should be achieved. Also, efficient harvesting of either morula stage pre-stem cells and/or stem cells isolated from the inner cell mass of blastocysts should be achieved. These embryonic pre-stem and stem cell populations should preferably remain viable in culture for more than one week.
  • Pluripotent stem cells will be isolated and directed to differentiate into hemopoietic destinies. Therefore, tissues derived from the blood cell group or beta cells of the immune response system will be replaced in deficient patients suffering from conditions such as HIV infection, post-chemotherapy, or irradiation depletion. Culture condition in vitro will direct the rate and degree of differentiation manifested by these pluripotent stem cells, such as the presence of "teacher cells” or certain additives to the media, e.g. cytokines.
  • stem cells will be modified by formation of chimeric cell lines that incorporate "hybrid" metabolic functions that when transplanted will provide the transplant recipient with long-term relief from organ/tissue deficiencies. For instance, the production of dopamine in situ can modify neurological treatments for patients manifesting muscular rigidity and loss of motor control in disease states such as Parkinson's disease. Unlike pharmaceutical therapeutics which are partially effective temporarily, transplantation of chimeric stem cells that regulate the production dopamine and serotonergic factors will offer these patients superior outcomes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Developmental Biology & Embryology (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Reproductive Health (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne un procédé qui permet d'isoler et de propager une lignée de cellules souches embryonnaires à partir du stade morula (pré-souche) ou blastocyste (souche à masse cellulaire interne (ICM)), pour les besoins des transplantations de cellules, de tissus ou d'organes.
PCT/US1999/004188 1998-02-27 1999-02-26 Derivation de cellules et de tissus a partir du stade cellulaire pre-souche pour les therapies de transplantation WO1999043785A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002320423A CA2320423A1 (fr) 1998-02-27 1999-02-26 Derivation de cellules et de tissus a partir du stade cellulaire pre-souche pour les therapies de transplantation
AU28799/99A AU757036B2 (en) 1998-02-27 1999-02-26 Derivation of cells and tissues from embryonic pre-stem cells for transplantation therapies
JP2000533525A JP2002504362A (ja) 1998-02-27 1999-02-26 移植治療のための前駆胚幹細胞からの細胞および組織の誘導体
EP99909633A EP1056835A4 (fr) 1998-02-27 1999-02-26 Derivation de cellules et de tissus a partir du stade cellulaire pre-souche pour les therapies de transplantation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7627398P 1998-02-27 1998-02-27
US60/076,273 1998-02-27

Publications (1)

Publication Number Publication Date
WO1999043785A1 true WO1999043785A1 (fr) 1999-09-02

Family

ID=22130951

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/004188 WO1999043785A1 (fr) 1998-02-27 1999-02-26 Derivation de cellules et de tissus a partir du stade cellulaire pre-souche pour les therapies de transplantation

Country Status (5)

Country Link
EP (1) EP1056835A4 (fr)
JP (1) JP2002504362A (fr)
AU (1) AU757036B2 (fr)
CA (1) CA2320423A1 (fr)
WO (1) WO1999043785A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003075648A1 (fr) * 2002-03-13 2003-09-18 Fundacion Ivi Para El Estudio De La Reproduccion Humana (Fivier) Methodes de production de lignees cellulaires
US6667176B1 (en) 2000-01-11 2003-12-23 Geron Corporation cDNA libraries reflecting gene expression during growth and differentiation of human pluripotent stem cells
EP1415661A1 (fr) * 2002-10-28 2004-05-06 Biosense, Inc. Cellules souches embryonnaires ciblant une zone dans les tissus pour l' administration des stimulateurs de translocation
US7250294B2 (en) 2000-05-17 2007-07-31 Geron Corporation Screening small molecule drugs using neural cells differentiated from human embryonic stem cells
US7297539B2 (en) 2000-01-11 2007-11-20 Geron Corporation Medium for growing human embryonic stem cells
US7455983B2 (en) 2000-01-11 2008-11-25 Geron Corporation Medium for growing human embryonic stem cells
US7763463B2 (en) 2000-05-17 2010-07-27 Geron Corporation Use of cyclic AMP and ascorbic acid to produce dopaminergic neurons from embryonic stem cells
US8148148B2 (en) 2000-05-17 2012-04-03 Geron Corporation Neural progenitor cell populations
US9074181B2 (en) 2005-06-22 2015-07-07 Asterias Biotherapeutics, Inc. Suspension culture of human embryonic stem cells

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5453366A (en) * 1990-07-26 1995-09-26 Sims; Michele M. Method of cloning bovine embryos

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9308271D0 (en) * 1993-04-21 1993-06-02 Univ Edinburgh Method of isolating and/or enriching and/or selectively propagating pluripotential animal cells and animals for use in said method
US5914268A (en) * 1994-11-21 1999-06-22 National Jewish Center For Immunology & Respiratory Medicine Embryonic cell populations and methods to isolate such populations

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5453366A (en) * 1990-07-26 1995-09-26 Sims; Michele M. Method of cloning bovine embryos

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
DINSMORE J., ET AL.: "EMBRYONIC STEM CELLS DIFFERENTIATED IN VITRO AS A NOVEL SOURCE OF CELLS FOR TRANSPLANTATION.", CELL TRANSPLANTATION, COGNIZANT COMMUNICATION CORP., US, vol. 05., no. 02., 1 January 1996 (1996-01-01), US, pages 131 - 143., XP002920536, ISSN: 0963-6897, DOI: 10.1016/0963-6897(95)02040-3 *
OKABE S., ET AL.: "DEVELOPMENT OF NEURONAL PRECURSOR CELLS AND FUNCTIONAL POSTMITOTIC NEURONS FROM EMBRYONIC STEM CELLS IN VITRO.", MECHANISMS OF DEVELOPMENT., ELSEVIER SCIENCE IRELAND LTD., IE, vol. 59., no. 01., 1 January 1996 (1996-01-01), IE, pages 89 - 102., XP000615956, ISSN: 0925-4773, DOI: 10.1016/0925-4773(96)00572-2 *
See also references of EP1056835A4 *
SHIM H., ET AL.: "ISOLATION OF PLURIPOTENT STEM CELLS FROM CULTURED PORCINE PRIMORDIAL GERM CELLS.", THERIOGENOLOGY, LOS ALTOS, CA, US, 1 January 1997 (1997-01-01), US, pages 245., XP000199312, ISSN: 0093-691X, DOI: 10.1016/S0093-691X(97)82372-2 *
SOTOMARU Y., ET AL.: "A COMPARATIVE INVESTIGATION ON THE POTENCY OF CELLS FROM THE INNER CELL MASS AND TROPHECTODERM OF MOUSE BLASTOCYSTS TO PRODUCE CHIMERAS.", THERIOGENOLOGY, LOS ALTOS, CA, US, vol. 48., 1 January 1997 (1997-01-01), US, pages 977 - 984., XP002920537, ISSN: 0093-691X, DOI: 10.1016/S0093-691X(97)00324-5 *
STRELCHENKO N.: "BOVINE PLURIPOTENT STEM CELLS.", THERIOGENOLOGY, LOS ALTOS, CA, US, vol. 45., 1 January 1996 (1996-01-01), US, pages 131 - 140., XP002920535, ISSN: 0093-691X, DOI: 10.1016/0093-691X(95)00362-C *
UCHIDA M., ET AL.: "EFFECTS OF FEEDER CELLS AND GROWTH FACTORS ON THE PROLIFERATION OF MOUSE PRIMORDIAL GERM CELLS.", THERIOGENOLOGY, LOS ALTOS, CA, US, vol. 44., 1 January 1995 (1995-01-01), US, pages 09 - 16., XP002920538, ISSN: 0093-691X, DOI: 10.1016/0093-691X(95)00143-V *

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8097458B2 (en) 1998-10-23 2012-01-17 Geron Corporation Micro-carrier culture system for rapid expansion of human embryonic stem cells
US10059939B2 (en) 1998-10-23 2018-08-28 Asterias Biotherapeutics, Inc. Screening methods for human embryonic stem cells
US8951800B2 (en) 1998-10-23 2015-02-10 Asterias Biotherapeutics, Inc. Primate pluripotent stem cell expansion without feeder cells and in the presence of FGF and matrigel or Engelbreth-Holm-Swarm tumor cell preparation
US8637311B2 (en) 1998-10-23 2014-01-28 Asterias Biotherapeutics, Inc. Human embryonic stem cells genetically modified to contain a nucleic acid and cultured with fibroblast growth factor
US7297539B2 (en) 2000-01-11 2007-11-20 Geron Corporation Medium for growing human embryonic stem cells
US7041438B2 (en) 2000-01-11 2006-05-09 Geron Corporation Use of human embryonic stem cells for drug screening and toxicity testing
US7455983B2 (en) 2000-01-11 2008-11-25 Geron Corporation Medium for growing human embryonic stem cells
US7560281B2 (en) 2000-01-11 2009-07-14 Geron Corporation Use of TGF beta superfamily antagonists to make dopaminergic neurons from embryonic stem cells
US10351821B2 (en) 2000-01-11 2019-07-16 Asterias Biotherapeutics Inc. Neural cell populations from primate pluripotent stem cells
US6667176B1 (en) 2000-01-11 2003-12-23 Geron Corporation cDNA libraries reflecting gene expression during growth and differentiation of human pluripotent stem cells
US9790466B2 (en) 2000-01-11 2017-10-17 Asterias Biotherapeutics, Inc. Neural cell populations from primate pluripotent stem cells
US8153428B2 (en) 2000-01-11 2012-04-10 Geron Corporation Use of TGF beta superfamily antagonists and neurotrophins to make neurons from embryonic stem cells
US8252586B2 (en) 2000-01-11 2012-08-28 Geron Corporation Neural cell populations from primate pluripotent stem cells
US7250294B2 (en) 2000-05-17 2007-07-31 Geron Corporation Screening small molecule drugs using neural cells differentiated from human embryonic stem cells
US8252585B2 (en) 2000-05-17 2012-08-28 Geron Corporation Neural progenitor cell populations
US8148148B2 (en) 2000-05-17 2012-04-03 Geron Corporation Neural progenitor cell populations
US9803174B2 (en) 2000-05-17 2017-10-31 Asterias Biotherapeutics, Inc. Neural progenitor cell populations
US7763463B2 (en) 2000-05-17 2010-07-27 Geron Corporation Use of cyclic AMP and ascorbic acid to produce dopaminergic neurons from embryonic stem cells
WO2003075648A1 (fr) * 2002-03-13 2003-09-18 Fundacion Ivi Para El Estudio De La Reproduccion Humana (Fivier) Methodes de production de lignees cellulaires
EP1415661A1 (fr) * 2002-10-28 2004-05-06 Biosense, Inc. Cellules souches embryonnaires ciblant une zone dans les tissus pour l' administration des stimulateurs de translocation
US9074181B2 (en) 2005-06-22 2015-07-07 Asterias Biotherapeutics, Inc. Suspension culture of human embryonic stem cells
US10676714B2 (en) 2005-06-22 2020-06-09 Asterias Biotherapeutics, Inc. Suspension culture of human embryonic stem cells

Also Published As

Publication number Publication date
EP1056835A1 (fr) 2000-12-06
AU757036B2 (en) 2003-01-30
CA2320423A1 (fr) 1999-09-02
AU2879999A (en) 1999-09-15
JP2002504362A (ja) 2002-02-12
EP1056835A4 (fr) 2003-01-15

Similar Documents

Publication Publication Date Title
Llames et al. Human plasma as a dermal scaffold for the generation of a completely autologous bioengineered skin
Homma et al. Induction of epithelial progenitors in vitro from mouse embryonic stem cells and application for reconstruction of damaged cornea in mice
US8071376B2 (en) Production of oligodendrocytes from placenta-derived stem cells
KR101335884B1 (ko) 망막 줄기 세포로부터 유래한 합성 각막
WO2000073421A2 (fr) Methodes d'isolement, de cryopreservation, et d'utilisation therapeutique de cellules epitheliales amniotiques humaines
CN101688177A (zh) 来自贴壁胎盘干细胞的肝细胞和软骨细胞；以及cd34+、cd45-胎盘干细胞富集的细胞群
Silva et al. Toward personalized cell therapies by using stem cells: seven relevant topics for safety and success in stem cell therapy
EP3243903A1 (fr) Procédé exempt d'alimentateur de culture de cellules souches spermatogoniales bovines et porcines
IL157392A (en) Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells
US20130302887A1 (en) Compositions and methods for growing human embryonic cells
AU757036B2 (en) Derivation of cells and tissues from embryonic pre-stem cells for transplantation therapies
Ghanbari et al. Novel therapeutic approaches of tissue engineering in male infertility
US20030143737A1 (en) Long-term cell-culture compositions and genetically modified animals derived therefrom
US20020159975A1 (en) Derivation of cells and tissues from embryonic pre-stem cells for transplantation therapies
CN109153963B (zh) 粘附状态的细胞培养物的改变方法
US20110263013A1 (en) Compositions And Methods For Growing Embryonic Stem Cells
US20060148079A1 (en) Isolation and purification of human insulin producing cells for the treatment of insulin dependent diabetes
US20110250236A1 (en) Stem cells derived from the carotid body and uses thereof
US20070207542A1 (en) Manipulation of oxygen tension during in vitro follicle culture
WO2009139881A2 (fr) Compositions et méthodes permettant de cultiver des cellules souches embryonnaires
AU779273B2 (en) Long-term cell culture compositions and genetically modified animals derived therefrom
Shpall et al. Transplantation of ex vivo expanded cord blood
Suckow et al. Tissue distribution of fetal liver cells following in utero transplantation in mice
Stewart Stem Cells and Stem Cell therapies: the Future for Regenerative Medicine?
Gurer et al. Therapeutic use of cloning: Osmangazi turk identical embryonic stem cells and embryonic stem cell transfer to diabetic mice

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP NO

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2320423

Country of ref document: CA

Ref country code: CA

Ref document number: 2320423

Kind code of ref document: A

Format of ref document f/p: F

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 533525

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1999909633

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 28799/99

Country of ref document: AU

WWP Wipo information: published in national office

Ref document number: 1999909633

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1999909633

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 28799/99

Country of ref document: AU

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载