[go: up one dir, main page]

WO2010042800A1 - Procédés de reprogrammation de cellules somatiques et procédés d'utilisation de telles cellules - Google Patents

Procédés de reprogrammation de cellules somatiques et procédés d'utilisation de telles cellules Download PDF

Info

Publication number
WO2010042800A1
WO2010042800A1 PCT/US2009/060138 US2009060138W WO2010042800A1 WO 2010042800 A1 WO2010042800 A1 WO 2010042800A1 US 2009060138 W US2009060138 W US 2009060138W WO 2010042800 A1 WO2010042800 A1 WO 2010042800A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
cell
sall4
ips
factor
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.)
Ceased
Application number
PCT/US2009/060138
Other languages
English (en)
Inventor
Yupo Ma
Dan Xu
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.)
Nevada Cancer Institute
Original Assignee
Nevada Cancer Institute
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 Nevada Cancer Institute filed Critical Nevada Cancer Institute
Publication of WO2010042800A1 publication Critical patent/WO2010042800A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
    • 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
    • C12N2500/44—Thiols, e.g. mercaptoethanol
    • 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
    • C12N2501/60—Transcription factors
    • 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
    • C12N2501/60—Transcription factors
    • C12N2501/602—Sox-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
    • C12N2501/60—Transcription factors
    • C12N2501/603—Oct-3/4
    • 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
    • C12N2501/60—Transcription factors
    • C12N2501/604—Klf-4
    • 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"
    • 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

  • hemophilia is characterized by spontaneous and prolonged hemorrhage that can result in disability and death.
  • the most common complication is chronic arthritis caused by bleeding within the joints. Traumatic injuries to individuals with hemophilia will cause rapid blood loss and, if not treated rapidly, will lead to death.
  • Current therapies include fixed-dose prophylaxis, protein replacement therapies, and most recently, gene therapies.
  • Current prophylaxis and protein replacements therapies are limited by incomplete efficacy, high cost, restricted availability and the possible development of neutralizing antibodies against Factor VIII in chronically treated individuals.
  • much of the clinical presentation in hemophilia patients can be relieved by expression of only 3% of wild-type clotting protein, and in most cases an individual with 30% of wild-type clotting factor would be phenotypically normal.
  • liver progenitor cells functionally integrated into the recipient liver expressed Factor IX and phenotypically corrected the mouse model.
  • Factor IX Factor IX
  • One option is to generate ES cell banks of cell lines carrying various HLA haplotypes.
  • the extremely broad variety of immune types within the heterogeneous US population is a disincentive for this approach, as are ethical issues surrounding sourcing and use of ES cells.
  • iPS cells exhibit morphological (i.e., round shape, large nucleoli and scant cytoplasm) and growth properties (i.e., doubling time; ES cells have a doubling time of about seventeen to eighteen hours) akin to ES cells.
  • iPS cells express pluripotent cell- specific markers (e.g., Oct-4, SSEA-3, SSEA-4, Tra-1-60, Tra-1-81, and SSEA-I).
  • pluripotent cell- specific markers e.g., Oct-4, SSEA-3, SSEA-4, Tra-1-60, Tra-1-81, and SSEA-I).
  • iPS cells are not immediately derived from embryos and can transiently or stably express one or more copies of selected potency-determining factors at least until they become pluripotent.
  • EBs are aggregates of ES cells or iPS cells that have passed through the first stage of embryonic development. That is, EBs have already made a lineage commitment to embryonic tissues and cannot generate extraembryonic trophectoderm. These experiments show that it is possible using the invention methods to generate EBs from fibroblast-derived iPS cells ( Figure 14). Although EBs have made an early lineage commitment, this does not affect their therapeutic potential because they can still generate all cell lineages of the developing embryo and particularly for the purposes of this example, endodermal lineages.
  • Liver precursor and mature cells were also derived from iPS cells expressing Factor VIII and liver-specific markers including alpha fetoprotein, albumin, CYPlAl and HNF-4a ( Figure 17).
  • EBs were digested into single cells and cultured as described in Example 1 except that the medium was supplemented with a mixture of cytokines and induction factors (FLT3 ligand, SCF, TPO thrombopoieitin, interferon-gamma, and VEGF) for 7 days.
  • FLT3 ligand, SCF, TPO thrombopoieitin, interferon-gamma, and VEGF cytokines and induction factors
  • H&E staining of the cells showed hematopoietic-like cells including erythroid cell precursors and neutrophils.
  • Flow cytometry analysis of the hematopoietic-like cells were positive for hematopoietic cell surface markers B220, Terl 19, Gr-I and CD34.
  • Tail-tip fibroblasts derived from C57BL/6 mice were cultured using growth medium containing High Glucose DMEM (Invitrogen), 10% certified FBS (Invitrogen) and IX pen strep (Invitrogen). Growth medium was changed every other day.
  • Plat-E retroviral packaging cells (Clontech) were cultured using growth medium containing RPMI 1640 (Invitrogen), 10% certified FBS (Invitrogen) and IX pen strep (Invitrogen). Growth medium was changed every other day.
  • OP9 stromal cells ATCC were cultured using growth medium containing alpha-MEM (Invitrogen), 20% certified FBS and IX pen strep. Growth medium was changed every other day.
  • Polybrene was added to the virus cocktail to enhance infection efficiency. Infection was performed overnight. Virus containing media was removed and replaced with fresh prewarmed growth media. The fibroblasts were allowed to recover for 8 hours. The second batch of viruses were collected, filtered and used instantly for re-infection. Infection was performed as previously. Infected cells were allowed to recover for 7 days. Media was changed every other day.
  • EB bodies from W4 ES and iPS cells were collected and digested into single cell suspension using 2mg/ml collagenase IV (Invitrogen). EB bodies were incubated for 20 minutes in collagenase IV at 37 0 C water bath. After incubation, cells were washed with enzyme-free dissociation medium (Invitrogen) and was triturated until suspension became homogenous. Cells were plated into gel coated MitomycinC-treated semi-confluent OP9 stromal cells using HoxB4 retrovirus and infection was performed overnight. Cells were then collected and virus containing medium was discarded.
  • enzyme-free dissociation medium Invitrogen
  • Colony forming unit assay was performed as previous described. Briefly, 2XlO "4 . CD34+/B220+/Terl 19+/Gr-l+/c-kit+ sorted cells were plated in low adherent 35mm culture dish (Stem Cell Technologies) with semi-solid methylcellulose medium M3434 (Stem Cell Technologies). Progenitor colonies were scored after 5 days.
  • mice were injected with anti-asialo GMl antibody (Wako) according to manufacturer's instructions.
  • Acute anemia was induced in 4-6 weeks old C57BL/6 mice using 50mg/ml Phenylhydrazine HCL. 3 days after injection, cells were injected intravenously with UlOT 6 CD34+/B220+/Terl l9+/Gr-l+/c-kit+ sorted.
  • Anti- asialo GMl antibody was continuously injected 1 day, 1 week and 2 weeks after transplantation.
  • EBs differenDay 32 ⁇ _g Begin differentiation of celts into hematopoietic cells by treatment tiated into - ⁇ ? of five cytokines FLT3L, SCF, TPO, ⁇ E ⁇ F,FN ⁇ hematopoietic Day 34 cells
  • iPS-derived islet-like clusters both human and mouse derived response to glucose-stimulated insulin secretion.
  • the islet-like clusters were sequentially treated with low (5.5mM Glucose with 5OuM Tolbutamide) and high (27.7 Glucose mM) concentrations of glucose.
  • low glucose concentration insulin was detected in all iPS types at comparable level.
  • high glucose concentration beta cells generated from human SALL4- ⁇ PS cells had a more robust response to glucose stimulation.
  • cardiac specific markers included alpha heavy chain cardiac myosin (alpha-MHC), cardiac ventricle myosin light chain(MLV-2v), atrial natriuretic factor (ANF) and pluripotent stem cell marker OCT4.
  • alpha-MHC alpha heavy chain cardiac myosin
  • MLV-2v cardiac ventricle myosin light chain
  • AMF atrial natriuretic factor
  • OCT4 pluripotent stem cell marker
  • Mouse fetal heart cDNA was used as control.
  • H9, W4 ES cells and both sall4 iPS cells express OCT4 highly indicating cells under pluripotent status.
  • Both human and mouse Sall4-iPS cells derived cardiomyocytes strongly expressed all the cardiac markers while no OCT4 expression ( Figure 2). This indicates that the iPS cells were successfully differentiated into mature cardiomycytes including ventricular and atrial cells.
  • EBs were then monitored on a daily basis up to 55 days of differentiation.
  • Day 22 shows stable attachment of EBs on the culture plate and cells on the edge of the plate continue to proliferate. More pronounced alveolar-like structures were observed at day 24th of differentiation.
  • mRNA expression of typical endoderm and mesoderm lung cell markers Brachyury, FoxA2, and Soxl7 were examined in the iPS-derived lung progenitor cells.
  • Results of qRT-PCR confirmed that iPS-derived cells expressed upregulated Brachyury, FoxA2, and Soxl 7 in the differentiation stage.
  • early and mature lung markers SPC, TTF-I and SPA, SPB, CClO 5 respectively, were analyzed to characterized the population of iPS-alveolar cells.
  • Results of qRT-PCR confirmed upregulation of early and mature lung makers, indicating a heterogeneous population.
  • iPS-alveolar cells from the final stage of lung differentiation was analyzed for early and mature lung markers and sorted by flow cytometry.
  • Flow cytometry analysis indicated upregulation of early markers SPC and TTF-I . Only mature lung marker SPB was stained while SPA could not be detected.
  • Lung disease is the 3 r leading killer in America and is responsible for 1 in 6 deaths.
  • Lung tissue is a uniquely specialized tissue in the body that can become irreversibly damaged by scarring and fibrosis that occur in cystic fibrosis (CF), emphysema, and sarcoidosis.
  • CF cystic fibrosis
  • emphysema emphysema
  • sarcoidosis sarcoidosis
  • ES embryonic stem cells
  • Lung-ES functional epithelial alveolar cells
  • Stage 1 conditions differentiate iPS cells into definitive endoderm and mesoderm layers in suspension
  • Stage 2 condition attaches the embryo-like (EB) structures to tissue culture dishes coated with gelatin
  • Stage 3 conditions further differentiate the EBs into Type II progenitor pneumocytes.
  • Well established early lung markers, Surfactant Protein C (SPC) and TTF-I were upregulated at all the time points tested.
  • Mature lung markers such SPA, SPB and CClO were upregulated as well demonstating heterogenous population of early and mature lung cells.
  • TTF-I mRNA expression was markedly upregulated. This data suggests an abundance of lung epithelial progenitor cells even at the very late stage of differentiation.
  • Wild type Tail-tip fibroblasts were used as the calibrator during analysis and cell suspension from lung from wild type mice were used as positive control.
  • Day 24 lung epithelial progenitor cells derived from 3F-iPS cells were tested: SPC and TTF-I early lung markers stained positive.
  • Mature lung markers SPA and SPB were also tested and only SPB stained positive comparable to the early marker counterparts.
  • Mature lung markers, SPA and SPB were slightly positive.
  • iPS cells (designated 3F-iPS for their 3 factor derivation), expressed typical pluripotent stem cell markers such as ES-alkaline phosphatase, SSEA-I, Nanog, Oct4 and SALL4.
  • 3F-iPS cells gave rise to teratomas composed of all germ layers within one month following injection.
  • Endothelial cells are thought to secrete the majority of FVIII protein in vivo.
  • 3F-iPS cells were cultured using a hanging drop method for 2 days in LIF-free media where they readily formed spheroid EBs. By this method, the generation of EBs devoid of extraembryonic characteristics was ensured. After 2 day culture in a hanging drop, the EBs were collected and transferred to a nonadherent Petri dish and allowed to differentiate for an additional 2 days.
  • VEGF vascular endothelial growth factor
  • the endothelial cells derived from 3F-iPS were analyzed by immunofluorescence using various markers: FIk-I, an early endothelial progenitor marker, CD31 and FVIII, markers commonly used for cells or tissues of vascular endothelial origin.
  • FIk-I an early endothelial progenitor marker
  • CD31 an early endothelial progenitor marker
  • FVIII markers commonly used for cells or tissues of vascular endothelial origin.
  • Early stages of endothelial cells differentiation (day 6) showed expression of FIk-I but not CD31 which indicate the presence of endothelial progenitor cells.
  • Mature endothelial differentiation stages at day 12 and 18 showed weak to no expression of FIk-I and strong expression of CD31.
  • the mature differentiated cells also expressed FVIII.
  • RT-PCR real-time PCR
  • Hemophilia A is a sex-linked bleeding disorder characterized by the deficiency of coagulation Factor VIII causing prolonged bleeding due to the inability to efficiently clot.
  • Treatment for hemophilia generally includes either fixed-dose prophylaxis or factor replacement therapy on an as needed basis. Regardless, neutralizing antibodies to the replacement protein have been reported and present a unique problem when treating hemophiliacs.
  • endothelial progenitor cells derived from iPS cells can effectively express the FVIII protein, engraft within the hepatic parenchyma, and functionally integrate to provide the therapeutic benefit necessary for phenotypic correction of hemophilia. It is interesting to note that while the iPS derived endothelial cells were injected into the liver; higher levels of FVIII mRNA were detected in spleen, heart and kidney tissues of injected animals. Additional studies of GFP-tagged epithelial cells will be required to establish the complete whole-body distribution.
  • virus- containing supernatant was collected for each transcription factor and combined with supplemental 8ul/mL polybrene (Chemicon, Billerica, MA). Medium was replenished and the transfected packaging cells were allowed to generate virus for an additional 24 hours. Filtered virus-containing supernatant was used to infect 2x10 5 tail-tip fibroblasts (TTF) from C57BL/6 mice at passage 3-4.
  • TTF tail-tip fibroblasts
  • 3F-iPS cells were harvested by 0.25% trypsin treatment, collected into tubes, centrifuged, and the pellets were resuspended in EB differentiation medium.
  • a lO 6 cell suspension in lOOul was mixed with an equal volume of Geltrex (Invitrogen, Carlsbad, CA) and injected subcutaneously into SCID mice (Jackson Laboratory, Bar Harbor, Maine). A total of 5 mice were injected.
  • teratoma were dissected and fixed with formalin (Fisher Scientific, Pittsburgh, PA). Paraffin-embedded tissue was sectioned and stained with hematoxylin and eosin.
  • the EBs were transferred to 35mm tissue culture dishes after 4 days of growth in EB differentiation medium and allowed to differentiate into endothelial progenitor cells using medium containing KDMEM, 15% fetal bovine serum (FBS), 2 mM L-Glutamine, IxIO "4 M nonessential amino acids, IxIO -4 M 2-mercaptoethanol, Ix pen/strep, 20ng/ml bFGF (Invitrogen, Carlsbad, CA), 20ng/ml EGF (Invitrogen, Carlsbad, CA), 50ng/ml VEGF (R&D Systems, Minneapolis, MN), 20ng/ml IGF (Sigma, St Louis, MO), 50ug/ml Ascorbic acid (Sigma, St Louis, MO) and lug/ml Hydrocortisone (Sigma, St Louis, MO).
  • endothelial progenitor cell differentiation cells were collected after 10 days of differentiation using Collagenase IV (Invitrogen, Carlsbad, CA) for identification and characterization.
  • Collagenase IV Invitrogen, Carlsbad, CA
  • mature endothelial cell differentiation cells were passaged using 0.25% trypsin (Invitrogen, Carlsbad, CA) and replated on collagen IV coated dishes using endothelial cell culture medium containing EGM-2 (Lonza, Portsmouth, NH), 15% FBS, 2 mM L-Glutamine, IxIO "4 M nonessential amino acids, IxIO -4 M 2-mercaptoethanol, Ix pen/strep, 20 ng/ml bFGF, 20ng/ml EGF, 50ng/ml VEGF, 20ng/ml IGF, 50ug/ml Ascorbic acid and lug/ml Hydrocortisone. Cells were passed when dishes were 90% confluent.
  • Hemophilia A mice (Jackson Laboratory, Strain Name: B6; 129S4- F8tmlKaz/J, Stock Number: 004424) 6-8 weeks old were used for this study(28). Hemophilia A mice were originally produced by disruption of the FVIII gene through insertion of a targeting vector containing a neomycin gene cassette in the 3' end of exon 16. The targeting vector was introduced into 129S4/SvJae-derived Jl embryonic stem (ES) cells and was injected into C57BL/6 blastocysts.
  • ES Jl embryonic stem
  • Somatic cell reprogramming to create induced pluripotent stem (iPS) cells has been accomplished by numerous laboratories using retrovirus transduction, expression plasmids and non-integrating adenovirus to introduce multiple transcription factors, notably Oct4, Sox2, Klf4, and c-Myc.
  • iPS induced pluripotent stem
  • Sall4 is encoded by a gene with important roles in early embryonic development and pluripotency maintenance.
  • Sall4 can regulate the transcriptional levels of Oct4, Sox2, Klf4 and c-Myc(13). This suggested that Sall4 may have potential utility in somatic cell reprogramming.
  • W4 ES cells and Sall4-iPS cells were positively stained for ES- alkaline phosphatase, an enzymatic marker of self renewal.
  • the cells were subjected to immunostaining with antibodies to Oct4, Sox2 and Nanog, all of which are known markers of pluripotent stem cells. Expression for each stem cell marker was positive, hi contrast, the surrounding fibroblasts did not stain positive for either of these proteins.
  • the levels of protein expression in Sall4-iPS cells were qualitatively similar to those expressed in the murine ES cell line W4. Surrounding feeder layer was used as an internal negative control and showed no detectable signals.
  • EBs embryoid bodies
  • Sall4-iPS cells For in vivo testing of pluripotency, we injected Sall4-iPS cells into the flanks of SCID/NOD mice to determine their pluripotent potential. When 5X10 6 mouse Sall4-iPS cells were introduced into adult immunodeficient SCID/NOD mice through subcutaneous injection, the cells spontaneously formed teratoma-like masses containing ectodermal, mesodermal, and endodermal tissue types. The presence of three germ layers in teratomas derived from the injection of mouse Sall4-iPS cells indicates the pluripotent characteristics of the cells.
  • the feeder cells were derived from a pool of day 13.5 embryos of CF-I mice were used for both mouse and human iPS cells as well as ES cells. These cells were maintained in High Glucose DMEM, 10% certified FBS and IX pen strep and were expanded up to passage 3. Confluent flasks were treated with 10 ug/ml mitomycin-C for 2.5 hrs. The cells were then washed 5 times with PBS and were collected by dissociation with 0.25% trypsin in PBS. Cells were then stored in freezing media containing 50% certified FBS, 40% High Glucose DMEM and 10% DMSO at -80 c until use.

Landscapes

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

Abstract

La présente invention porte sur un procédé de reprogrammation de cellules somatiques de primate par exposition d'une cellule somatique de primate à SALL4 dans des conditions suffisantes pour reprogrammer les cellules ; et de culture des cellules exposées pour obtenir des cellules reprogrammées. On peut utiliser les cellules obtenues par les procédés de l'invention en tant que compositions pharmaceutiques dans des contextes cliniques, par exemple, le traitement de l'hémophilie A chez un sujet.
PCT/US2009/060138 2008-10-10 2009-10-09 Procédés de reprogrammation de cellules somatiques et procédés d'utilisation de telles cellules Ceased WO2010042800A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10467108P 2008-10-10 2008-10-10
US61/104,671 2008-10-10
US11692008P 2008-11-21 2008-11-21
US61/116,920 2008-11-21

Publications (1)

Publication Number Publication Date
WO2010042800A1 true WO2010042800A1 (fr) 2010-04-15

Family

ID=42100968

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/060138 Ceased WO2010042800A1 (fr) 2008-10-10 2009-10-09 Procédés de reprogrammation de cellules somatiques et procédés d'utilisation de telles cellules

Country Status (1)

Country Link
WO (1) WO2010042800A1 (fr)

Cited By (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011109837A3 (fr) * 2010-03-05 2011-12-15 Yupo Ma Procédés et compositions pour le traitement du diabète au moyen de cellules pancréatiques de type bêta dérivées d'ips
WO2013058403A1 (fr) 2011-10-21 2013-04-25 国立大学法人京都大学 Méthode de culture de cellules individuellement dispersées et maintenues pluripotentes au moyen d'un flux laminaire
WO2013077423A1 (fr) 2011-11-25 2013-05-30 国立大学法人京都大学 Procédé pour la culture de cellules souches pluripotentes
WO2013111515A1 (fr) * 2012-01-23 2013-08-01 国立大学法人 東京大学 Procédé d'induction/activation d'une cellule souche/progénitrice cardiaque à l'aide d'un facteur spécifique
EP2609193A4 (fr) * 2010-08-23 2014-02-26 Univ New York State Res Found Procédé d'expansion de cellules souches et utilisation de telles cellules
WO2014123242A1 (fr) 2013-02-08 2014-08-14 国立大学法人京都大学 Procédés de production de mégacaryocytes et de plaquettes
WO2014136581A1 (fr) 2013-03-06 2014-09-12 国立大学法人京都大学 Système de culture pour des cellules souches pluripotentes et procédé pour la sous-culture de cellules souches pluripotentes
WO2014148646A1 (fr) 2013-03-21 2014-09-25 国立大学法人京都大学 Cellule souche pluripotente pour l'induction de la différenciation neuronale
WO2014157257A1 (fr) 2013-03-25 2014-10-02 公益財団法人先端医療振興財団 Procédé de tri cellulaire
WO2014168264A1 (fr) 2013-04-12 2014-10-16 国立大学法人京都大学 Procédé pour l'induction de cellules progénitrices d'épithélium alvéolaire
WO2014185358A1 (fr) 2013-05-14 2014-11-20 国立大学法人京都大学 Procédé efficace d'induction de cellules myocardiques
WO2014192909A1 (fr) 2013-05-31 2014-12-04 ｉＨｅａｒｔ Ｊａｐａｎ株式会社 Plaque de cellules stratifiée comprenant un hydrogel
WO2014200115A1 (fr) 2013-06-11 2014-12-18 国立大学法人京都大学 Procédé de production de cellules précurseurs rénales et médicament contenant des cellules précurseurs rénales
WO2015020113A1 (fr) 2013-08-07 2015-02-12 国立大学法人京都大学 Méthode de production de cellule productrice d'hormone pancréatique
WO2015034012A1 (fr) 2013-09-05 2015-03-12 国立大学法人京都大学 Nouveau procédé pour l'induction de cellules précurseurs neurales produisant de la dopamine
WO2015064754A1 (fr) 2013-11-01 2015-05-07 国立大学法人京都大学 Nouveau procédé d'induction de chondrocytes
EP3081638A1 (fr) 2015-04-16 2016-10-19 Kyoto University Procédé de production de pseudo-îlots
WO2016183593A3 (fr) * 2015-05-14 2017-03-09 The Regents Of The University Of California Thérapie prénatale
US9783783B2 (en) 2013-01-30 2017-10-10 Cornell University Compositions and methods for the expansion of stem cells
WO2017183736A1 (fr) 2016-04-22 2017-10-26 国立大学法人京都大学 Procédé de production de cellules précurseurs neurales produisant de la dopamine
EP3305899A1 (fr) 2011-07-25 2018-04-11 Kyoto University Procédé de criblage de cellules souches pluripotentes induites
WO2018124118A1 (fr) 2016-12-27 2018-07-05 住友化学株式会社 Procédé d'évaluation et procédé de sélection de cellules souches pluripotentes induites, et procédé de fabrication de cellules souches pluripotentes induites
WO2018135646A1 (fr) 2017-01-20 2018-07-26 国立大学法人京都大学 PROCÉDÉ DE PRODUCTION DE LYMPHOCYTES T CD8α+β+ CYTOTOXIQUES
WO2018139548A1 (fr) 2017-01-26 2018-08-02 国立大学法人大阪大学 Milieu destiné à induire une différenciation de cellules souches en cellules mésodermiques et procédé destiné à produire des cellules mésodermiques
WO2018168829A1 (fr) 2017-03-14 2018-09-20 国立大学法人京都大学 Procédé de production de lymphocytes t auxiliaires à partir de cellules souches pluripotentes
WO2018216743A1 (fr) 2017-05-25 2018-11-29 国立大学法人京都大学 Méthode pour induire la différenciation d'une cellule mésodermique intermédiaire en une cellule progénitrice rénale, et méthode pour induire la différenciation d'une cellule souche pluripotente en une cellule progénitrice rénale
WO2018235583A1 (fr) 2017-06-19 2018-12-27 公益財団法人神戸医療産業都市推進機構 Procédé de prévision de capacité de différenciation de cellules souches pluripotentes, et réactif associé
WO2019078263A1 (fr) 2017-10-17 2019-04-25 国立大学法人京都大学 Procédé d'obtention de jonction neuromusculaire artificielle à partir de cellules souches pluripotentes
WO2020013315A1 (fr) 2018-07-13 2020-01-16 国立大学法人京都大学 PROCÉDÉ DE PRODUCTION DE LYMPHOCYTES T γδ
WO2020017575A1 (fr) 2018-07-19 2020-01-23 国立大学法人京都大学 Cartilage en forme de plaque dérivé de cellules souches pluripotentes et procédé de production de cartilage en forme de plaque
WO2020022261A1 (fr) 2018-07-23 2020-01-30 国立大学法人京都大学 Nouveau marqueur de cellule progénitrice rénale et méthode de concentration de cellules progénitrices rénales l'utilisant
WO2020116606A1 (fr) 2018-12-06 2020-06-11 キリンホールディングス株式会社 Procédé de production de lymphocytes t ou de cellules nk, milieu de culture de lymphocytes t ou de cellules nk, procédé de culture de lymphocytes t ou de cellules nk, procédé de maintien de l'état indifférencié de lymphocytes t indifférenciés, et agent d'accélération de croissance pour lymphocytes t ou cellules nk
WO2020130147A1 (fr) 2018-12-21 2020-06-25 国立大学法人京都大学 Tissu de type cartilage à lubricine localisée, procédé pour sa production et composition le comprenant pour le traitement de lésions du cartilage articulaire
WO2020138371A1 (fr) 2018-12-26 2020-07-02 キリンホールディングス株式会社 Tcr modifié et son procédé de production
US10711249B2 (en) 2014-12-26 2020-07-14 Kyoto University Method for inducing hepatocytes
WO2020230832A1 (fr) 2019-05-15 2020-11-19 味の素株式会社 Procédé de purification de cellules de crête neurale ou de cellules épithéliales cornéennes
WO2020235319A1 (fr) 2019-05-20 2020-11-26 味の素株式会社 Procédé de culture d'expansion pour cellules précurseurs de cartilage ou d'os
WO2021117886A1 (fr) 2019-12-12 2021-06-17 国立大学法人千葉大学 Préparation lyophilisée contenant des mégacaryocytes et des plaquettes
WO2021174004A1 (fr) 2020-02-28 2021-09-02 Millennium Pharmaceuticals, Inc. Procédé de production de cellules tueuses naturelles à partir de cellules souches pluripotentes
WO2021256522A1 (fr) 2020-06-17 2021-12-23 国立大学法人京都大学 Cellules immunocompétentes exprimant un récepteur antigénique chimérique
EP3929302A1 (fr) 2014-07-14 2021-12-29 Chugai Seiyaku Kabushiki Kaisha Procédé d'identification d'un épitope sur une protéine
WO2022014604A1 (fr) 2020-07-13 2022-01-20 国立大学法人京都大学 Cellules précurseurs de muscle squelettique et procédé de purification de celles-ci, composition pour le traitement de maladies myogènes et procédé de production d'un groupe de cellules contenant des cellules précurseurs de muscle squelettique
WO2022019152A1 (fr) 2020-07-20 2022-01-27 学校法人 愛知医科大学 Composition pour la culture d'entretien indifférenciée de cellules pluripotentes, milieu pour la culture d'entretien indifférenciée de cellules pluripotentes, procédé de culture d'entretien à l'état indifférencié de cellules pluripotentes, et procédé de production de cellules pluripotentes
WO2022039279A1 (fr) 2020-08-18 2022-02-24 国立大学法人京都大学 Procédé de maintien et d'amplification de cellules germinales primordiales humaines/cellules du type cellules germinales primordiales humaines
US11401504B2 (en) 2016-04-15 2022-08-02 Kyoto University Method for inducing antigen specific CD8 positive T cells
WO2022196714A1 (fr) 2021-03-17 2022-09-22 アステラス製薬株式会社 Péricyte ayant un gène de facteur de croissance fibroblastique basique (bfgf) introduit dans celui-ci
WO2022230977A1 (fr) 2021-04-30 2022-11-03 国立研究開発法人理化学研究所 Agrégat sous forme de cordon de cellules de l'épithélium pigmentaire rétinien, dispositif ainsi que procédé de fabrication de celui-ci, et remède comprenant cet agrégat sous forme de cordon
WO2022255489A1 (fr) 2021-06-04 2022-12-08 キリンホールディングス株式会社 Composition cellulaire, procédé de production de la composition cellulaire, et composition pharmaceutique contenant la composition cellulaire
WO2022259721A1 (fr) 2021-06-10 2022-12-15 味の素株式会社 Procédé de production de cellules souches mésenchymateuses
WO2022264033A1 (fr) 2021-06-15 2022-12-22 Takeda Pharmaceutical Company Limited Procédé de production de cellules tueuses naturelles à partir de cellules souches pluripotentes
WO2023286832A1 (fr) 2021-07-15 2023-01-19 アステラス製薬株式会社 Cellules de type péricyte exprimant le facteur de croissance endothéliale vasculaire (vegf) à un niveau élevé
WO2023286834A1 (fr) 2021-07-15 2023-01-19 アステラス製薬株式会社 Cellule de type péricyte exprimant le facteur de croissance endothéliale vasculaire (vegf) à un niveau élevé
WO2023017848A1 (fr) 2021-08-11 2023-02-16 国立大学法人京都大学 Procédé de production de cellules progénitrices interstitielles rénales, cellules produisant de l'érythropoïétine et procédé de production de cellules produisant de la rénine
WO2023085356A1 (fr) 2021-11-11 2023-05-19 株式会社ヘリオス Cellule souche pluripotente génétiquement modifiée, cellule immunocompétente dérivée, procédé de production de ces cellules et utilisation associée
WO2023153464A1 (fr) 2022-02-09 2023-08-17 住友ファーマ株式会社 Procédé d'évaluation du potentiel de différenciation de cellules dans un bouillon de culture dans la différenciation de cellules souches pluripotentes en cellules neurales de la région de plaque de plancher mésencéphale
WO2023210713A1 (fr) 2022-04-27 2023-11-02 国立大学法人京都大学 Promoteur de régénération de cellules épicardiques et procédé pour favoriser la régénération de cellules épicardiques
WO2023238932A1 (fr) 2022-06-10 2023-12-14 国立大学法人京都大学 Procédé et réactif de détection pour cellules souches pluripotentes indifférenciées
WO2024248023A1 (fr) 2023-05-29 2024-12-05 京都府公立大学法人 Procédé de production d'organoïde du noyau suprachiasmatiqu
WO2024248157A1 (fr) 2023-05-31 2024-12-05 学校法人順天堂 Lymphocytes t cd4-positifs dérivés de cellules souches pluripotentes, leur procédé de production et leur utilisation
WO2024248017A1 (fr) 2023-05-29 2024-12-05 国立研究開発法人理化学研究所 Procédé de maturation de cardiomyocytes et procédé de production de cardiomyocytes matures
US12241089B2 (en) 2014-07-18 2025-03-04 Kyoto University Method for inducing t cells for cell-based immunotherapy from pluripotent stem cells

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030049236A1 (en) * 2001-07-27 2003-03-13 Arhus Amt Immortalized stem cells
US20040033214A1 (en) * 1999-09-24 2004-02-19 Young Henry E. Pluripotent embryonic-like stem cells, compositions, methods and uses thereof
US20080070303A1 (en) * 2005-11-21 2008-03-20 West Michael D Methods to accelerate the isolation of novel cell strains from pluripotent stem cells and cells obtained thereby
US20080187514A1 (en) * 2000-07-31 2008-08-07 Piero Anversa Methods and Compositions for the Repair and/or Regeneration of Damaged Myocardium
US20080233610A1 (en) * 2007-03-23 2008-09-25 Thomson James A Somatic cell reprogramming
US20080241110A1 (en) * 2005-11-29 2008-10-02 Nevada Cancer Institute Targeting of sall4 for the treatment and diagnosis of proliferative disorders associated with myelodysplastic syndrome (MDS)

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040033214A1 (en) * 1999-09-24 2004-02-19 Young Henry E. Pluripotent embryonic-like stem cells, compositions, methods and uses thereof
US20080187514A1 (en) * 2000-07-31 2008-08-07 Piero Anversa Methods and Compositions for the Repair and/or Regeneration of Damaged Myocardium
US20030049236A1 (en) * 2001-07-27 2003-03-13 Arhus Amt Immortalized stem cells
US20080070303A1 (en) * 2005-11-21 2008-03-20 West Michael D Methods to accelerate the isolation of novel cell strains from pluripotent stem cells and cells obtained thereby
US20080241110A1 (en) * 2005-11-29 2008-10-02 Nevada Cancer Institute Targeting of sall4 for the treatment and diagnosis of proliferative disorders associated with myelodysplastic syndrome (MDS)
US20080233610A1 (en) * 2007-03-23 2008-09-25 Thomson James A Somatic cell reprogramming

Cited By (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011109837A3 (fr) * 2010-03-05 2011-12-15 Yupo Ma Procédés et compositions pour le traitement du diabète au moyen de cellules pancréatiques de type bêta dérivées d'ips
EP2609193A4 (fr) * 2010-08-23 2014-02-26 Univ New York State Res Found Procédé d'expansion de cellules souches et utilisation de telles cellules
US9309496B2 (en) 2010-08-23 2016-04-12 The Research Foundation For The State University Of New York Method for expansion of stem cells and the use of such cells
EP3608423A1 (fr) 2011-07-25 2020-02-12 Kyoto University Procédé de criblage de cellules souches pluripotentes induites
EP3305899A1 (fr) 2011-07-25 2018-04-11 Kyoto University Procédé de criblage de cellules souches pluripotentes induites
WO2013058403A1 (fr) 2011-10-21 2013-04-25 国立大学法人京都大学 Méthode de culture de cellules individuellement dispersées et maintenues pluripotentes au moyen d'un flux laminaire
WO2013077423A1 (fr) 2011-11-25 2013-05-30 国立大学法人京都大学 Procédé pour la culture de cellules souches pluripotentes
WO2013111515A1 (fr) * 2012-01-23 2013-08-01 国立大学法人 東京大学 Procédé d'induction/activation d'une cellule souche/progénitrice cardiaque à l'aide d'un facteur spécifique
US9783783B2 (en) 2013-01-30 2017-10-10 Cornell University Compositions and methods for the expansion of stem cells
WO2014123242A1 (fr) 2013-02-08 2014-08-14 国立大学法人京都大学 Procédés de production de mégacaryocytes et de plaquettes
WO2014136581A1 (fr) 2013-03-06 2014-09-12 国立大学法人京都大学 Système de culture pour des cellules souches pluripotentes et procédé pour la sous-culture de cellules souches pluripotentes
WO2014148646A1 (fr) 2013-03-21 2014-09-25 国立大学法人京都大学 Cellule souche pluripotente pour l'induction de la différenciation neuronale
WO2014157257A1 (fr) 2013-03-25 2014-10-02 公益財団法人先端医療振興財団 Procédé de tri cellulaire
WO2014168264A1 (fr) 2013-04-12 2014-10-16 国立大学法人京都大学 Procédé pour l'induction de cellules progénitrices d'épithélium alvéolaire
WO2014185358A1 (fr) 2013-05-14 2014-11-20 国立大学法人京都大学 Procédé efficace d'induction de cellules myocardiques
WO2014192909A1 (fr) 2013-05-31 2014-12-04 ｉＨｅａｒｔ Ｊａｐａｎ株式会社 Plaque de cellules stratifiée comprenant un hydrogel
WO2014200115A1 (fr) 2013-06-11 2014-12-18 国立大学法人京都大学 Procédé de production de cellules précurseurs rénales et médicament contenant des cellules précurseurs rénales
WO2015020113A1 (fr) 2013-08-07 2015-02-12 国立大学法人京都大学 Méthode de production de cellule productrice d'hormone pancréatique
US9796962B2 (en) 2013-08-07 2017-10-24 Kyoto University Method for generating pancreatic hormone-producing cells
WO2015034012A1 (fr) 2013-09-05 2015-03-12 国立大学法人京都大学 Nouveau procédé pour l'induction de cellules précurseurs neurales produisant de la dopamine
WO2015064754A1 (fr) 2013-11-01 2015-05-07 国立大学法人京都大学 Nouveau procédé d'induction de chondrocytes
EP3929302A1 (fr) 2014-07-14 2021-12-29 Chugai Seiyaku Kabushiki Kaisha Procédé d'identification d'un épitope sur une protéine
US12241089B2 (en) 2014-07-18 2025-03-04 Kyoto University Method for inducing t cells for cell-based immunotherapy from pluripotent stem cells
US10711249B2 (en) 2014-12-26 2020-07-14 Kyoto University Method for inducing hepatocytes
EP3081638A1 (fr) 2015-04-16 2016-10-19 Kyoto University Procédé de production de pseudo-îlots
WO2016183593A3 (fr) * 2015-05-14 2017-03-09 The Regents Of The University Of California Thérapie prénatale
US12391921B2 (en) 2016-04-15 2025-08-19 Kyoto University Method for inducing antigen specific CD8 positive T cells
US11401504B2 (en) 2016-04-15 2022-08-02 Kyoto University Method for inducing antigen specific CD8 positive T cells
WO2017183736A1 (fr) 2016-04-22 2017-10-26 国立大学法人京都大学 Procédé de production de cellules précurseurs neurales produisant de la dopamine
WO2018124118A1 (fr) 2016-12-27 2018-07-05 住友化学株式会社 Procédé d'évaluation et procédé de sélection de cellules souches pluripotentes induites, et procédé de fabrication de cellules souches pluripotentes induites
EP4053268A2 (fr) 2017-01-20 2022-09-07 Kyoto University Procédé de production de lymphocytes t cd8alpha+beta+cytotoxiques
WO2018135646A1 (fr) 2017-01-20 2018-07-26 国立大学法人京都大学 PROCÉDÉ DE PRODUCTION DE LYMPHOCYTES T CD8α+β+ CYTOTOXIQUES
WO2018139548A1 (fr) 2017-01-26 2018-08-02 国立大学法人大阪大学 Milieu destiné à induire une différenciation de cellules souches en cellules mésodermiques et procédé destiné à produire des cellules mésodermiques
WO2018168829A1 (fr) 2017-03-14 2018-09-20 国立大学法人京都大学 Procédé de production de lymphocytes t auxiliaires à partir de cellules souches pluripotentes
WO2018216743A1 (fr) 2017-05-25 2018-11-29 国立大学法人京都大学 Méthode pour induire la différenciation d'une cellule mésodermique intermédiaire en une cellule progénitrice rénale, et méthode pour induire la différenciation d'une cellule souche pluripotente en une cellule progénitrice rénale
WO2018235583A1 (fr) 2017-06-19 2018-12-27 公益財団法人神戸医療産業都市推進機構 Procédé de prévision de capacité de différenciation de cellules souches pluripotentes, et réactif associé
WO2019078263A1 (fr) 2017-10-17 2019-04-25 国立大学法人京都大学 Procédé d'obtention de jonction neuromusculaire artificielle à partir de cellules souches pluripotentes
WO2020013315A1 (fr) 2018-07-13 2020-01-16 国立大学法人京都大学 PROCÉDÉ DE PRODUCTION DE LYMPHOCYTES T γδ
WO2020017575A1 (fr) 2018-07-19 2020-01-23 国立大学法人京都大学 Cartilage en forme de plaque dérivé de cellules souches pluripotentes et procédé de production de cartilage en forme de plaque
WO2020022261A1 (fr) 2018-07-23 2020-01-30 国立大学法人京都大学 Nouveau marqueur de cellule progénitrice rénale et méthode de concentration de cellules progénitrices rénales l'utilisant
WO2020116606A1 (fr) 2018-12-06 2020-06-11 キリンホールディングス株式会社 Procédé de production de lymphocytes t ou de cellules nk, milieu de culture de lymphocytes t ou de cellules nk, procédé de culture de lymphocytes t ou de cellules nk, procédé de maintien de l'état indifférencié de lymphocytes t indifférenciés, et agent d'accélération de croissance pour lymphocytes t ou cellules nk
WO2020130147A1 (fr) 2018-12-21 2020-06-25 国立大学法人京都大学 Tissu de type cartilage à lubricine localisée, procédé pour sa production et composition le comprenant pour le traitement de lésions du cartilage articulaire
WO2020138371A1 (fr) 2018-12-26 2020-07-02 キリンホールディングス株式会社 Tcr modifié et son procédé de production
WO2020230832A1 (fr) 2019-05-15 2020-11-19 味の素株式会社 Procédé de purification de cellules de crête neurale ou de cellules épithéliales cornéennes
WO2020235319A1 (fr) 2019-05-20 2020-11-26 味の素株式会社 Procédé de culture d'expansion pour cellules précurseurs de cartilage ou d'os
WO2021117886A1 (fr) 2019-12-12 2021-06-17 国立大学法人千葉大学 Préparation lyophilisée contenant des mégacaryocytes et des plaquettes
WO2021174004A1 (fr) 2020-02-28 2021-09-02 Millennium Pharmaceuticals, Inc. Procédé de production de cellules tueuses naturelles à partir de cellules souches pluripotentes
WO2021256522A1 (fr) 2020-06-17 2021-12-23 国立大学法人京都大学 Cellules immunocompétentes exprimant un récepteur antigénique chimérique
WO2022014604A1 (fr) 2020-07-13 2022-01-20 国立大学法人京都大学 Cellules précurseurs de muscle squelettique et procédé de purification de celles-ci, composition pour le traitement de maladies myogènes et procédé de production d'un groupe de cellules contenant des cellules précurseurs de muscle squelettique
WO2022019152A1 (fr) 2020-07-20 2022-01-27 学校法人 愛知医科大学 Composition pour la culture d'entretien indifférenciée de cellules pluripotentes, milieu pour la culture d'entretien indifférenciée de cellules pluripotentes, procédé de culture d'entretien à l'état indifférencié de cellules pluripotentes, et procédé de production de cellules pluripotentes
WO2022039279A1 (fr) 2020-08-18 2022-02-24 国立大学法人京都大学 Procédé de maintien et d'amplification de cellules germinales primordiales humaines/cellules du type cellules germinales primordiales humaines
WO2022196714A1 (fr) 2021-03-17 2022-09-22 アステラス製薬株式会社 Péricyte ayant un gène de facteur de croissance fibroblastique basique (bfgf) introduit dans celui-ci
WO2022230977A1 (fr) 2021-04-30 2022-11-03 国立研究開発法人理化学研究所 Agrégat sous forme de cordon de cellules de l'épithélium pigmentaire rétinien, dispositif ainsi que procédé de fabrication de celui-ci, et remède comprenant cet agrégat sous forme de cordon
WO2022255489A1 (fr) 2021-06-04 2022-12-08 キリンホールディングス株式会社 Composition cellulaire, procédé de production de la composition cellulaire, et composition pharmaceutique contenant la composition cellulaire
WO2022259721A1 (fr) 2021-06-10 2022-12-15 味の素株式会社 Procédé de production de cellules souches mésenchymateuses
WO2022264033A1 (fr) 2021-06-15 2022-12-22 Takeda Pharmaceutical Company Limited Procédé de production de cellules tueuses naturelles à partir de cellules souches pluripotentes
WO2023286834A1 (fr) 2021-07-15 2023-01-19 アステラス製薬株式会社 Cellule de type péricyte exprimant le facteur de croissance endothéliale vasculaire (vegf) à un niveau élevé
WO2023286832A1 (fr) 2021-07-15 2023-01-19 アステラス製薬株式会社 Cellules de type péricyte exprimant le facteur de croissance endothéliale vasculaire (vegf) à un niveau élevé
WO2023017848A1 (fr) 2021-08-11 2023-02-16 国立大学法人京都大学 Procédé de production de cellules progénitrices interstitielles rénales, cellules produisant de l'érythropoïétine et procédé de production de cellules produisant de la rénine
WO2023085356A1 (fr) 2021-11-11 2023-05-19 株式会社ヘリオス Cellule souche pluripotente génétiquement modifiée, cellule immunocompétente dérivée, procédé de production de ces cellules et utilisation associée
WO2023153464A1 (fr) 2022-02-09 2023-08-17 住友ファーマ株式会社 Procédé d'évaluation du potentiel de différenciation de cellules dans un bouillon de culture dans la différenciation de cellules souches pluripotentes en cellules neurales de la région de plaque de plancher mésencéphale
WO2023210713A1 (fr) 2022-04-27 2023-11-02 国立大学法人京都大学 Promoteur de régénération de cellules épicardiques et procédé pour favoriser la régénération de cellules épicardiques
WO2023238932A1 (fr) 2022-06-10 2023-12-14 国立大学法人京都大学 Procédé et réactif de détection pour cellules souches pluripotentes indifférenciées
WO2024248023A1 (fr) 2023-05-29 2024-12-05 京都府公立大学法人 Procédé de production d'organoïde du noyau suprachiasmatiqu
WO2024248017A1 (fr) 2023-05-29 2024-12-05 国立研究開発法人理化学研究所 Procédé de maturation de cardiomyocytes et procédé de production de cardiomyocytes matures
WO2024248157A1 (fr) 2023-05-31 2024-12-05 学校法人順天堂 Lymphocytes t cd4-positifs dérivés de cellules souches pluripotentes, leur procédé de production et leur utilisation

Similar Documents

Publication Publication Date Title
WO2010042800A1 (fr) Procédés de reprogrammation de cellules somatiques et procédés d'utilisation de telles cellules
CA2823265C (fr) Procede de generation de cellules souches pluripotentes induites et de cellules differenciees
Sánchez-Danés et al. Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells
Lu et al. A defined xeno-free and feeder-free culture system for the derivation, expansion and direct differentiation of transgene-free patient-specific induced pluripotent stem cells
Egusa et al. Gingival fibroblasts as a promising source of induced pluripotent stem cells
Montserrat et al. Generation of pig iPS cells: a model for cell therapy
JP5813321B2 (ja) 体細胞の再プログラム化
CN102190731B (zh) 用人工转录因子诱导产生多能干细胞
DK2455452T3 (en) PLURIPOTENT STEM CELLS THAT CAN BE ISOLATED FROM BODY TISSUE
JP6603529B2 (ja) 再プログラム化多能性細胞の作製
CN101864392A (zh) 核重新编程因子
EP2513297B1 (fr) Matériels et méthodes pour la production de cellules souches pluripotentes
Sgodda et al. Improved hepatic differentiation strategies for human induced pluripotent stem cells
EP2481795A1 (fr) Procédé de génération de cellules souches pluripotentes induites et des cellules différentiées
US10190097B2 (en) Method and composition for inducing human pluripotent stem cells
US20210340495A1 (en) Method for inducing and differentiating pluripotent stem cells and uses thereof
Huang et al. Induced pluripotent stem cell technologies for tissue engineering
WO2010033969A1 (fr) Cellules pluripotentes dérivées du liquide amniotique
KR20100097969A (ko) 인간 대동맥 평활근 세포로부터 제조된 유도성 전능 줄기세포
Xu et al. Induced Pluripotent Stem Cells: Proliferation, Migration, MicroRNA, Signaling Molecules
GRACE Generation of Porcine Induced Pluripotent Stem Cells and their Differentiation into Cardiac Lineages
Zhang iPSC-Derived MSCs that Are Genetically Engineered for Systemic Bone Augmentation
HK1176639B (en) Materials and methods for generating pluripotent stem cells

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09819934

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09819934

Country of ref document: EP

Kind code of ref document: A1