EP1341915A1 - Utilisation de cellules derivees de cellules souches embryonnaires pour augmenter la tolerance aux transplantations et pour regenerer un tissu altere - Google Patents

Utilisation de cellules derivees de cellules souches embryonnaires pour augmenter la tolerance aux transplantations et pour regenerer un tissu altere

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Publication number
EP1341915A1
EP1341915A1 EP01995556A EP01995556A EP1341915A1 EP 1341915 A1 EP1341915 A1 EP 1341915A1 EP 01995556 A EP01995556 A EP 01995556A EP 01995556 A EP01995556 A EP 01995556A EP 1341915 A1 EP1341915 A1 EP 1341915A1
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EP
European Patent Office
Prior art keywords
cells
ecl
specific
donor
cell
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP01995556A
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German (de)
English (en)
Inventor
Michael Bader
Bert Binas
Giuxuan Chai
Fred FÄNDRICH
Detlev Ganten
Xiongbin Lin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Original Assignee
Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
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Application filed by Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft filed Critical Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Publication of EP1341915A1 publication Critical patent/EP1341915A1/fr
Withdrawn legal-status Critical Current

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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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0271—Chimeric vertebrates, e.g. comprising exogenous cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • 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
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/02—Animal zootechnically ameliorated
    • A01K2267/025—Animal producing cells or organs for transplantation
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0381—Animal model for diseases of the hematopoietic 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
    • A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5156—Animal cells expressing foreign proteins
    • 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
    • C12N2510/00—Genetically modified cells

Definitions

  • the invention relates to the use of cells from cell lines, which are derived from early embryonic stages, for the donor-specific increase of the transplant tolerance and for the restoration of destroyed tissue. Areas of application of the invention are medicine and the pharmaceutical industry.
  • tolerance immune tolerance
  • AG specific antigen
  • tolerance can be defined as persistent tissue persistence in the absence of a deleterious immune response that can be achieved without ongoing therapeutic intervention.
  • tolerance is not an innate characteristic of an individual, but is acquired (Owen, Science 102: 400-401, 1945; Billingham et al., Nature 172: 603-606, 1953). It is also known that the tolerant state that exists at birth changes constantly, especially when the body is confronted with new antigens in the course of life.
  • the immune system must be able to tolerate certain "foreign" antigens, such as physiological hormones released during puberty and pregnancy (Fowlkes and Ramsdell, Curr. Opin. Immunol. 5: 873-879, 1993).
  • fetal life can develop and survive in a host that is not adapted to major histocompatibility complex (MHC) is another example of nature's ability to distinguish not only between foreign and non-foreign, but also between dangerous and harmless can (Vacchio and Jiang, Grit. Rev. Immunol. 19: 461-480, 1999).
  • the invention is based on the object of generating a donor-specific immune tolerance in order to prevent rejection of the transplanted tissue by an immune reaction and thus to be able to restrict the administration of immunosuppressive agents.
  • ECL embryonic stem cell-like cell lines
  • the use of the cells from the ECLs as "tolerance vectors" is opened by a lack of MHC antigen expression and the associated immunogenic inactivity of the ECL.
  • Research has shown that cells from ECLs can be transplanted and survive in the long term, producing hematopoietic cells of different origins.
  • these hematopoietic cells derived from ECL have generated a constant mixed chimerism (donor and recipient hematopoietic cells coexist in the same host) and thus create the basis for long-term allograft acceptance. As a result, they can either be used as an ideal means of creating tolerance, or alternatively they can be used in a situation in which the parenchymal injury of a particular organ has to be remedied.
  • WKY Wistar Kyoto
  • SD Sprague Dawley
  • ACI ACI
  • WKY blastocysts grew very rapidly, showed strong primary growth, and more than 10% of the embryos achieved permanent cell lines (Table 1).
  • SD blastocysts grew with some delay, achieved a moderate number of primary clumps, and the effectiveness of cell line generation was poor.
  • ACI blastocysts took the longest time to grow, produced a very small number of primary clumps, and no cell line could be generated by this breed.
  • the use of the cells from the cell lines, which were generated from the embryonic stem cells, as "tolerance vectors" to bring about donor-specific immune tolerance also requires the expression of the donor-specific MHC antigens.
  • This property is achieved according to the invention in that cells of the ECLs are transfected with the genes of the donor which code for the MHC antigens.
  • the administration of the transfected cells e.g. via the portal vein, by intraperitoneal, subcutaneous or intravenous injection.
  • Mouse embryo fibroblasts (MEF) or rat embryo fibroblasts (REF) are prepared from 13-14 day pregnant animals that have been mitotically inactivated by 3-5 treatments with mitomycin C (10 ⁇ g / ml) for 2 or 1 hours, washed with phosphate buffered saline ( PBS) and planted in Nunc 4-wells.
  • mitomycin C 10 ⁇ g / ml
  • PBS phosphate buffered saline
  • the blastocysts are flushed with PBS / 20% FCS (fetal calf serum) or a culture medium from the uterus of rats 4.5 days pregnant, planted on inactivated embryo fibroblasts and 3-4 days in DMEM / 15% FCS / 2,500 ⁇ / ml LIF ( "Leukemia inhibiting factor", ESGRO, Life Technologies) with additives (Iannaccone et al, Dev. Biol. 1994; 163: 288-292) left untreated in a medium of 6% CO 2 / air.
  • the blastocysts develop and tie themselves to the supplier, and the ICM begins to grow, with the Efficiency depends on the genetic background.
  • Outgrowths with an ES-cell-like appearance are picked up and broken up into several lumps by suction in drawn glass capillaries with a somewhat smaller diameter than the outgrowths and applied to fresh supply plates. Picking up and breaking up occurs either daily or every other day. Crumbled colonies are reset in rows until a small number of clean, steadily growing ES-like clumps are obtained. The clump population is then expanded to several dozen, stored in 35 mm dishes and slightly trypsinized into a mixture of individual cells and small aggregates. The rat ES cells produced were passaged every or every other day by trypsinization (0.05% trypsin, 0.02% EDTA-4Na, 1% chicken serum, in Ca / Mg-free PBS). The species identity of the resulting cell lines is checked by PCR using Renin gene primers (Brenin et al., Transplant. Proc. 1997; 29: 1761-1765) in order to rule out contamination by mouse ES cells.
  • a first series of experiments examined the fate of a single intraportal injection of WKY-derived 1.0 x 10 6 ECL into allogeneic DA (RTl. Avl ) host rats that had received no immunosuppressive or myeloablative treatment.
  • the investigations show that these cells can survive long-term (> 150 days) in DA host rats. It was found that the ECL and its descendants can produce a state of constantly mixed chimerism (hematopoietic cells of the donor and the recipient coexist in the same host). It was also found that these cells differentiate into hematopoietic cells that express class II MHC antigens (Ox-3) and B cell lineage markers (Ox-45).
  • the monoclonal antibody (mAb) Ox-3 is a specific antibody of a (WKY) MHC class II donor that binds to class II MHC epitopes that are expressed on WKY but not to DA MHC positive cells class II.
  • WB double-stained leukocytes
  • Ox-3 + cells were detected histomorphologically (10-15%) in the interstitial space of the recipient (DA) hearts, which were selectively destroyed 100 days after a single intraportal injection of 1.0 x 10 6 ECL derived from WKY (see Fig.l).
  • the stable chimeric state of these animals provides the basis for examining the fate of the WKY cardiac allograft transplanted in DA rats seven days after the intraportal ECL injection.
  • Kaplan Meier diagrams show that pretreatment of DA rats with 1.0 x 10 6 ECL intraportally and heart transplantation (HTx) seven days later led to long-term (> 150 days) non-rejection allograft acceptance, whereas untreated DA rats caused WKY Reject allografts acutely (see Fig. 2).
  • CAP rat heart transplants were rejected from DA rats injected with WKY-ECL within 12.4 ⁇ 1.4 days, demonstrating the immune competence of these rats.
  • ECL cells described above assume differentiation into astrocytes or cardiomyocytes and hepatocytes by co-cultivation with somatic cells of neuronal or entodermal origin.
  • the embryonic cell lines described are therefore also suitable for the treatment of organ-specific diseases of the central nervous system (e.g. as dopaminergic cells for the treatment of Parkinson's disease, as hepatocytes for the treatment of cirrhosis of the liver or as cardiomyocytes for the treatment of fresh heart attacks).
  • organ-specific diseases of the central nervous system e.g. as dopaminergic cells for the treatment of Parkinson's disease, as hepatocytes for the treatment of cirrhosis of the liver or as cardiomyocytes for the treatment of fresh heart attacks.
  • the forthcoming isolation of the signal proteins necessary for these specific forms of differentiation is of great clinical importance, since it could enable problem-free programming of the ECLs for the desired cell population.
  • the goal is therefore the exact sequencing of these functional proteins in order to enable their recombinant production.
  • the large sequence homology between rat and human protein would also provide information on the analog production of human functional proteins.
  • the associated therapeutic application possibilities include both the use of the ECL-derived somatic cell lines described above and the functional proteins derived therefrom for future clinical use on all indication levels of tissue engineering for organ replacement, for gene therapy and for the treatment of metabolic diseases in the area of the CNS, the liver and the heart.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Wood Science & Technology (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Environmental Sciences (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Developmental Biology & Embryology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Transplantation (AREA)
  • Toxicology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Husbandry (AREA)
  • Cardiology (AREA)
  • Physics & Mathematics (AREA)
  • Mycology (AREA)

Abstract

L'invention concerne l'utilisation de cellules issues de lignes cellulaires, qui sont dérivées de stades embryonnaires précoces, pour augmenter de manière spécifique du donneur la tolérance aux transplantations et pour régénérer le tissu altéré. L'invention s'utilise en médecine et dans l'industrie pharmaceutique. L'invention vise à produire une immunotolérance spécifique du donneur pour empêcher un rejet du tissu transplanté par immunoréaction et à limiter par voie de conséquence l'administration d'immunodépresseurs. Pour produire une immunotolérance spécifique du donneur, des lignes cellulaires de type cellules souches embryonnaires (embryonic stem cell like cell lines, ECL) sont dérivées de blastocytes et transfectées avec le matériel génétique du donneur, qui code les haplotypes du MHC. Les cellules ainsi produites sont ensuite administrées au receveur avant la transplantation pour produire une immunotolérance vis-à-vis du tissu à transplanter ou pour régénérer le tissu d'ores et déjà altéré.
EP01995556A 2000-12-04 2001-12-04 Utilisation de cellules derivees de cellules souches embryonnaires pour augmenter la tolerance aux transplantations et pour regenerer un tissu altere Withdrawn EP1341915A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10061334A DE10061334A1 (de) 2000-12-04 2000-12-04 Verwendung von aus embryonalen Stammzellen hergeleiteten Zellen zur Erhöhung der Transplantationstoleranz und zur Wiederherstellung zerstörten Gewebes
DE10061334 2000-12-04
PCT/DE2001/004512 WO2002046401A1 (fr) 2000-12-04 2001-12-04 Utilisation de cellules derivees de cellules souches embryonnaires pour augmenter la tolerance aux transplantations et pour regenerer un tissu altere

Publications (1)

Publication Number Publication Date
EP1341915A1 true EP1341915A1 (fr) 2003-09-10

Family

ID=7666451

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01995556A Withdrawn EP1341915A1 (fr) 2000-12-04 2001-12-04 Utilisation de cellules derivees de cellules souches embryonnaires pour augmenter la tolerance aux transplantations et pour regenerer un tissu altere

Country Status (5)

Country Link
US (1) US20040208857A1 (fr)
EP (1) EP1341915A1 (fr)
JP (1) JP2004519437A (fr)
DE (1) DE10061334A1 (fr)
WO (1) WO2002046401A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002239294B2 (en) * 2000-11-22 2006-05-11 Asterias Biotherapeutics, Inc. Tolerizing allografts of pluripotent stem cells
US20040224403A1 (en) * 2001-12-07 2004-11-11 Robarts Research Institute Reconstituting hematopoietic cell function using human embryonic stem cells
US7799324B2 (en) 2001-12-07 2010-09-21 Geron Corporation Using undifferentiated embryonic stem cells to control the immune system
CN1630716A (zh) * 2001-12-07 2005-06-22 杰龙公司 人胚胎干细胞衍生的造血细胞
DE10362002B4 (de) 2003-06-23 2006-10-12 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Adulte pluripotente Stammzellen
EP1576957A1 (fr) * 2004-03-18 2005-09-21 Universiteit Twente Utilisations de cellules pluripotentes pour la réparation des tissus
JP6830674B2 (ja) 2017-01-25 2021-02-17 国立大学法人 東京大学 キメラ動物における出生後の炎症の発見とその治療

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11510698A (ja) * 1995-08-04 1999-09-21 ザ ジェネラル ホスピタル コーポレイション トランスジェニックブタ及びヒトｈｌａ遺伝子を有するブタ細胞
FR2760023B1 (fr) * 1997-02-21 2004-05-07 Commissariat Energie Atomique Cellules eucaryotes exprimant a leur surface au moins une isoforme d'hla-g et leurs applications
AU6869198A (en) * 1997-03-25 1998-10-20 Morphogenesis, Inc. Universal stem cells
CA2342205A1 (fr) * 1998-09-01 2000-03-09 Wisconsin Alumni Research Foundation Cellules souches embryonnaires de primates a genes d'histocompatibilite compatibles
US7544355B2 (en) * 2002-03-13 2009-06-09 Universita Degli Studi Di Perugia Methods and compositions for allogeneic transplantation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0246401A1 *

Also Published As

Publication number Publication date
DE10061334A1 (de) 2002-06-13
US20040208857A1 (en) 2004-10-21
WO2002046401A1 (fr) 2002-06-13
JP2004519437A (ja) 2004-07-02

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