+

WO2012007725A2 - Procédé de reprogrammation d'une cellule - Google Patents

Procédé de reprogrammation d'une cellule Download PDF

Info

Publication number
WO2012007725A2
WO2012007725A2 PCT/GB2011/001063 GB2011001063W WO2012007725A2 WO 2012007725 A2 WO2012007725 A2 WO 2012007725A2 GB 2011001063 W GB2011001063 W GB 2011001063W WO 2012007725 A2 WO2012007725 A2 WO 2012007725A2
Authority
WO
WIPO (PCT)
Prior art keywords
cell
inhibitor
cra
cimp
cells
Prior art date
Application number
PCT/GB2011/001063
Other languages
English (en)
Other versions
WO2012007725A3 (fr
Inventor
Yen Choo
Mylvaganam Jeyakumar
Original Assignee
Plasticell Ltd
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 Plasticell Ltd filed Critical Plasticell Ltd
Publication of WO2012007725A2 publication Critical patent/WO2012007725A2/fr
Publication of WO2012007725A3 publication Critical patent/WO2012007725A3/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
    • C12N5/0696—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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/065—Modulators of histone acetylation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/30—Hormones
    • C12N2501/38—Hormones with nuclear receptors
    • C12N2501/385—Hormones with nuclear receptors of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
    • 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
    • C12N2501/40—Regulators of development
    • 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
    • C12N2501/40—Regulators of development
    • C12N2501/48—Regulators of apoptosis
    • 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
    • C12N2501/70—Enzymes
    • C12N2501/71—Oxidoreductases (EC 1.)
    • 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
    • C12N2501/70—Enzymes
    • C12N2501/72—Transferases [EC 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
    • C12N2501/70—Enzymes
    • C12N2501/72—Transferases [EC 2.]
    • C12N2501/727—Kinases (EC 2.7.)
    • 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
    • C12N2501/999—Small molecules not provided for elsewhere
    • 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
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/08—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from cells of the nervous system
    • 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
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
    • C12N2506/1307—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from adult fibroblasts

Definitions

  • said CIMP cell is expanded , preferably, wherein said expanded CIMP cell is a population of homogenous cells.
  • the one or more pluripotency genes that have been induced by the addition of one or more CRA(s) is selected from the group consisting of alkaline phosphatase (ALP), SSEA1 , Oct4 or Nanog or a combination of two or more thereof - such as ALP and SSEA1 ; ALP and Oct4; ALP and Nanog; ALP, SSEA1 and Oct4; ALP, SSEA1 and Nanog; SSEA1 , Oct4 and Nanog; Oct4, ALP and Nanog.
  • ALP alkaline phosphatase
  • genes have been found to be associated with pluripotency and include, but are not limited to, Oct3/4, Sox-2, HDAC1 1 , Klf-4, Myc, Lin28 and Nanog.
  • the CRA(s) may be placed in contact with the cell for at least about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 16 hours, about 24 hours, about 36 hours, about 48 hours, about 60 hours, about 72 hours, about 84 hours, about 96 hours, about 108 hours or about 120 hours, suitably, at least about 24 to 72 hours, more suitably, at least about 48 to 72 hours, or more suitably, at least about 72 hours to induce CIMP cell formation.
  • one or more CRA(s) are contacted with a cell for about 24 hours, followed by an interval time of about 48 hours in the absence of CRA(s) used to reprogram the cells, followed by incubation with one or more (of the same or different) CRA(s) for about 24 hours, followed by an interval of about 48 hours without CRA(s) used to reprogram the cells, followed by incubation with one or more (of the same or different) CRA(s) for about 24 hours, followed by an interval time of about 48 hours in the absence of CRA(s) used to reprogram the cells.
  • Examples of chemicals for CIMP induction include but are not limited to Dexamethasone, Sinomenine, Flurbprofen, Theanine, 1 5d-PGJ2, Compound P, Ciglitazone, trans-2-Phenyl- cyclopropylamine (CPL), cyclic Pifithrin-a (PFT), 5-aza-2'-deoxycytidine, valproic acid, TTNPB, Y-27632, BIX01294, Phenytoin, Folic acid, Trichostatin A and/or Phenytoin and derivatives thereof or a combination of two or more thereof.
  • CPL trans-2-Phenyl- cyclopropylamine
  • PFT cyclic Pifithrin-a
  • 5-aza-2'-deoxycytidine 5-aza-2'-deoxycytidine
  • valproic acid TTNPB
  • Y-27632 Y-27632
  • BIX01294 Phenytoin
  • 5-aza-2'-deoxycytidine (5-AZA)
  • CRA(s) eg. all CRA(s)
  • the exposure in the presence of the chemicals may be for about 1 , 2 or 3 or more days at a time.
  • the exposure in the absence of the chemicals may be for about 1 , 2 or 3, 4,, 5 or 6 or more days at a time.
  • HDAC Inhibitor III M344
  • a PPAR gamma agonist eg. Ciglitazone
  • a retinoic acid receptor agonist eg. TTNPB
  • a caspase-3 Inhibitor eg. caspase-3 Inhibitor VII
  • a xanthine oxidase inhibitor eg. 3,5,7,8- tetrazabicyclo[4.3.0] nona-3,5,9-trien-2-one (allopurinol)
  • a H2 histamine receptor antagonist eg . Ranitidine
  • the method comprises contacting the cell with a combination of CRA(s) comprising, consisting or consisting essentially of a demethylating agent (eg. 5-aza-2'- deoxycytidine (5-AZA)); a KLF4 inducer (eg. 15d-PGJ2); an NADPH oxidase inhibitor (eg. Sinomenine) ; and a HDAC1 inhibitor (eg. valproic acid); incubating the cell in the absence of one or more CRA(s) (eg. all CRA(s)) for one or more days; contacting the cell with a combination of CRA(s) comprising, consisting or consisting essentially of a demethylating agent (eg.
  • a demethylating agent eg. 5-aza-2'- deoxycytidine (5-AZA)
  • a KLF4 inducer eg. 15d-PGJ2
  • an NADPH oxidase inhibitor eg. Sinomenine
  • HDAC1 inhibitor eg
  • the combination comprising, consisting or consisting essentially of a DNA methyltransferase inhibitor; a histone deacetylase inhibitor; a KLF4 inducer, a retinoic acid receptor agonist; an HDAC1 inhibitor; and a protein tyrosine phosphatase PTP inhibitor may be used together with a combination comprising, consisting or consisting essentially of a histone deacetylase inhibitor; a KLF4 inducer, a MEK/ERK inhibitor; a protein tyrosine phosphatase PTP inhibitor; a H2 histamine receptor antagonist and Pregnant mare serum Gonadotropin (PMSG).
  • PMSG Pregnant mare serum Gonadotropin
  • a method for identifying one or CRA(s) for reprogramming a cell into an CIMP cell comprising the steps of: (i) providing a cell; (ii) incubating said cell in the presence of: a combination of two or more chemicals; and/or a repetition of one or more of the same or different chemicals; and (iii) determining if said cell has been reprogrammed in to a CIMP cell, optionally, wherein said cell is incubated in the absence of the chemicals for a period of time; and wherein the presence of a CIMP cell is indicative that the one or more chemicals are able to reprogram the cell.
  • the CIMP cells described herein may undergo specialisation.
  • the CIMP cells may undergo further specialisation into one or more semi-differentiated or differentiated cells.
  • the CIMP cell undergoes further specialisation such that it is a more lineage restricted cell than the CIMP cell.
  • Protocols and kits for specialising (eg. differentiating) cells are available in the art.
  • a cell of the ectoderm lineage may be reprogrammed into a CIMP cell and then further differentiated into, for example, cells of the hematopoietic lineage - such as megakaryocytes, plasma cells, and/or macrophages/monocytes.
  • a further aspect relates to a method of reprogramming a cell of the mesoderm lineage via a CIMP cell comprising the steps of: (i) providing a cell of the mesoderm lineage; (ii) contacting said cell with one or more of the CRA(s) (eg. combinations of CRA(s)) described herein; (iii) obtaining a CIMP cell; (iv) differentiating the CIMP cell in to a desired cell type - such as an adipocyte/lipocyte, a bone cell (eg.
  • the cell culture conditions used in Combinatorial Cell Culture comprised bioactive chemical compounds with activities such as epigenetic modifi cation activities and effects on intracellular signal transduction.
  • the set of chemicals with epigenetic modu lation activity included chromatin modifying agents - such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, histone methyltransferase inhibitors and ATP dependent chromatin remodelling agents.
  • the set of chemicals with effects on intracellular signal transduction included chemicals known to modulate pathways that intersect with the signal transduction mechanism of Nanog, Klf4, PI3K, MEK/ERK, telomerase; GPR, Wnt, RAR, Calcium signalling, anti-appoptotic compounds, and other intracellular effectors.
  • iSTEM medium is said to eliminate differentiation signals to sustain mouse ES cell self-renewal and maintain stem cells in their ground state via blocking exogenous signals (to pERK) rather than providing exogenous signals to STAT3 via LIF.
  • ESGRO is a completely defined (serum-free) medium containing BMP4 and LIF that has been shown to support mouse ES cells under feeder-free and serum-free conditions (Ying et a/., 2003, Cell 1 15:281 -292). This enabled selective expansion of CIMP cells in cell units bearing such cells.
  • bead cultures were trypsinized, cells detached from the beads were further propagated as monolayer cultures in gelatine coated dishes.
  • the cells were, then stained with primary antibodies against beta- tubulin III (Sigma) and/or GFAP (Sigma), followed by staining with suitable secondary antibod ies conjugated to Alexa Fluor 488 or Alexa Fluor 594 (Invitrogen) . Nuclei were counterstained with Hoechst dye or DAPI (Invitrogen). Cells were imaged using a Nikon Eclipse TE 2000-S inverted fluorescence microscope equipped with Nikon DS-F1 1 camera.
  • NSC cells seeded on 170,000 gelatin beads were initially split (split 1 ) into 20 different media containing cocktails of CRA(s) and cultured therein for one day, then transferred to mES medium for a further two days.
  • cell units were washed in 10 volumes of DMEM and then pooled and split (split 2) into 15 different media containing cocktails of CRA(s) and cultured therein for one day, then transferred to mES medium for a further two days.
  • a method of reprogramming a cell into a chemically induced multi-lineage potential (CIMP) cell comprising the steps of: (i) contacting the cell to be reprogrammed with a medium comprising one or more chemical reprogramming agents (CRAs); and (ii) obtaining a CIMP cell, wherein the cell to be reprogrammed has not been genetically manipulated and/or contacted with one or more exogenous reprogramming proteins or nucleic acids encoding same to induce pluripotency.
  • CIMP chemically induced multi-lineage potential

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 That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne un procédé de reprogrammation d'une cellule par le biais d'une cellule de potentiel multilignée à induction chimique (CIMP pour chemically induced multi-lineage potential) comprenant les étapes consistant à :(i) mettre la cellule à reprogrammer en contact avec un milieu comprenant un ou plusieurs, de préférence, deux agents de reprogrammation chimique ou plus ; (ii) obtenir une cellule CIMP dans laquelle l'expression d'un ou plusieurs gènes de pluripotence est induite et une ou plusieurs protéines de pluripotence sont exprimées par le ou les gènes de pluripotence après contact avec le ou les agents de reprogrammation chimiques de telle sorte que la cellule a gagné de la puissance et la capacité de se différentier en un nombre accru de types de cellules par comparaison avec la cellule de l'étape (i) ; et (iii) différentier la cellule CIMP en une cellule à la lignée plus restreinte, de préférence, la cellule à reprogrammer n'ayant pas été génétiquement manipulée pour induire la pluripotence et/ou mise en contact avec une ou plusieurs protéines reprogrammatrices exogènes ou acides nucléiques les codant pour induire la pluripotence.
PCT/GB2011/001063 2010-07-16 2011-07-14 Procédé de reprogrammation d'une cellule WO2012007725A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US36492810P 2010-07-16 2010-07-16
US61/364,928 2010-07-16

Publications (2)

Publication Number Publication Date
WO2012007725A2 true WO2012007725A2 (fr) 2012-01-19
WO2012007725A3 WO2012007725A3 (fr) 2012-03-08

Family

ID=44629478

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2011/001063 WO2012007725A2 (fr) 2010-07-16 2011-07-14 Procédé de reprogrammation d'une cellule

Country Status (1)

Country Link
WO (1) WO2012007725A2 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103877595A (zh) * 2014-03-21 2014-06-25 中国科学院生物物理研究所 人类免疫缺陷病毒抑制剂或药物增敏剂的筛选方法
WO2013159091A3 (fr) * 2012-04-20 2015-04-30 Aptamir Therapeutics, Inc. Modulateurs de microarn de la thermogenèse
US9034839B2 (en) 2012-04-20 2015-05-19 Aptamir Therapeutics, Inc. miRNA modulators of thermogenesis
WO2015104424A1 (fr) * 2014-01-13 2015-07-16 Centre Leon Berard Procede de preparation de cellules pluripotentes induites
KR102087084B1 (ko) * 2020-02-03 2020-03-10 주식회사 이에이치엘바이오 항노화인자를 발현하는 지방유래 줄기세포의 대량 배양방법
CN117904034A (zh) * 2024-01-19 2024-04-19 杏林医学科技(江苏)有限公司 自体干细胞培养液及其在修复女性生殖器官凝胶上的应用
US12286625B2 (en) 2016-04-29 2025-04-29 Aptamir Therapeutics, Inc. Inhibition of mir-22 miRNA by APT-110

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997011366A1 (fr) 1995-09-20 1997-03-27 Merck & Co., Inc. Histone desacetylase comme cible pour des agents antiprotozoaires
US5990479A (en) 1997-11-25 1999-11-23 Regents Of The University Of California Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes
US6207392B1 (en) 1997-11-25 2001-03-27 The Regents Of The University Of California Semiconductor nanocrystal probes for biological applications and process for making and using such probes
US6251303B1 (en) 1998-09-18 2001-06-26 Massachusetts Institute Of Technology Water-soluble fluorescent nanocrystals
US6322901B1 (en) 1997-11-13 2001-11-27 Massachusetts Institute Of Technology Highly luminescent color-selective nano-crystalline materials
US20020045045A1 (en) 2000-10-13 2002-04-18 Adams Edward William Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media
US6426513B1 (en) 1998-09-18 2002-07-30 Massachusetts Institute Of Technology Water-soluble thiol-capped nanocrystals
US20030017264A1 (en) 2001-07-20 2003-01-23 Treadway Joseph A. Luminescent nanoparticles and methods for their preparation
US6576291B2 (en) 2000-12-08 2003-06-10 Massachusetts Institute Of Technology Preparation of nanocrystallites
WO2004031369A1 (fr) 2002-10-03 2004-04-15 Yen Choo Culture cellulaire
WO2004103136A1 (fr) 2003-05-20 2004-12-02 Claudia Barba-Vergara Dispositif manuel pour l'hygiene personnelle
US20090253203A1 (en) 2005-08-01 2009-10-08 Nupotential, Inc. Reprogramming a Cell by Inducing a Pluripotent Gene Through Use of a Small Molecule Modulator

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009102983A2 (fr) * 2008-02-15 2009-08-20 President And Fellows Of Harvard College Induction efficace de cellules souches multipotentes à l’aide de composés à petites molécules
WO2009117439A2 (fr) * 2008-03-17 2009-09-24 The Scripps Research Institute Approches chimiques et génétiques combinées pour la génération de cellules souches pluripotentes induites
WO2010056831A2 (fr) * 2008-11-12 2010-05-20 Nupotential, Inc. Reprogrammation d'une cellule par induction d'un gène pluripotent à l'aide d'un modulateur de hdac
US9045737B2 (en) * 2008-12-13 2015-06-02 Dnamicroarray, Inc. Artificial three-dimensional microenvironment niche culture
WO2011022413A2 (fr) * 2009-08-18 2011-02-24 Nupotential, Inc. Reprogrammation de cellule par activation du réseau de facteur de transcription endogène

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997011366A1 (fr) 1995-09-20 1997-03-27 Merck & Co., Inc. Histone desacetylase comme cible pour des agents antiprotozoaires
US6322901B1 (en) 1997-11-13 2001-11-27 Massachusetts Institute Of Technology Highly luminescent color-selective nano-crystalline materials
US5990479A (en) 1997-11-25 1999-11-23 Regents Of The University Of California Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes
US6207392B1 (en) 1997-11-25 2001-03-27 The Regents Of The University Of California Semiconductor nanocrystal probes for biological applications and process for making and using such probes
US6423551B1 (en) 1997-11-25 2002-07-23 The Regents Of The University Of California Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes
US6444143B2 (en) 1998-09-18 2002-09-03 Massachusetts Institute Of Technology Water-soluble fluorescent nanocrystals
US6319426B1 (en) 1998-09-18 2001-11-20 Massachusetts Institute Of Technology Water-soluble fluorescent semiconductor nanocrystals
US6426513B1 (en) 1998-09-18 2002-07-30 Massachusetts Institute Of Technology Water-soluble thiol-capped nanocrystals
US6251303B1 (en) 1998-09-18 2001-06-26 Massachusetts Institute Of Technology Water-soluble fluorescent nanocrystals
US20020045045A1 (en) 2000-10-13 2002-04-18 Adams Edward William Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media
US6576291B2 (en) 2000-12-08 2003-06-10 Massachusetts Institute Of Technology Preparation of nanocrystallites
US20030017264A1 (en) 2001-07-20 2003-01-23 Treadway Joseph A. Luminescent nanoparticles and methods for their preparation
WO2004031369A1 (fr) 2002-10-03 2004-04-15 Yen Choo Culture cellulaire
WO2004103136A1 (fr) 2003-05-20 2004-12-02 Claudia Barba-Vergara Dispositif manuel pour l'hygiene personnelle
US20090253203A1 (en) 2005-08-01 2009-10-08 Nupotential, Inc. Reprogramming a Cell by Inducing a Pluripotent Gene Through Use of a Small Molecule Modulator

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
"Appendix E of Stem Cells : Scientific Progress and Future Research Directions", June 2001, DEPARTMENT OF HEALTH AND HUMAN SERVICES
"Oligonucleotide Synthesis: A Practical Approach", 1984, IRL PRESS
"Remington's Pharmaceutical Sciences", 1985, MACK PUBLISHING CO.
AUSUBEL, F. M. ET AL.: "Current Protocols in Molecular Biology", 1995, JOHN WILEY & SONS
B. ROE, J. CRABTREE, A. KAHN: "DNA Isolation and Sequencing: Essential Techniques", 1996, JOHN WILEY & SONS
BERGE ET AL., J. PHARM. SCI., vol. 66, 1977, pages 1 - 19
BERGE ET AL., J.PHARM.SCI., vol. 66, 1977, pages 1 - 19
D. M. J. LILLEY, J. E. DAHLBERG: "Methods of Enzymology: DNA Structure Part A: Synthesis and Physical Analysis of DNA Methods in Enzymology", 1992, ACADEMIC PRESS
DAVIS PB, COOPER MJ., AAPS J., vol. 9, no. 1, 2007, pages E11 - 7
GUILES ET AL., ANGEW. CHEM. INTL ED ENGL, vol. 37, 1998, pages 926
HANNA, J. ET AL., SCIENCE, vol. 318, no. 5858, 2007, pages 1920 - 3
HOGAN, B., R. BEDDINGTON ET AL.: "Manipulating the Mouse Embryo: A Laboratory Manual", 1994, COLD SPRING HARBOUR PRESS
ICHIDA JK ET AL., CELL STEM CELL, vol. 5, 2009, pages 491 - 503
J. SAMBROOK, E. F. FRITSCH, T. MANIATIS: "Molecular Cloning: A Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
JONES GE, WISE CJ: "Establishment, maintenance, and cloning of human dermal fibroblasts", METHODS MOL BIOL., vol. 75, 1997, pages 13 - 21
LI S, MA Z, CURR GENE THER., 2001, pages 201 - 26
NICOLAOU ET AL., ANGEW CHEM INTL ED ENGL, vol. 34, 1995, pages 2289
SCIENCE, vol. 294, 2001, pages 137 - 141
SNYDER, CELL, vol. 68, 1992, pages 33 - 51
TAKAHASHI, K. ET AL., CELL, vol. 131, 2007, pages 861 - 872
TAKAHASHI, K. ET AL., CELL, vol. 131, no. 5, 2007, pages 861 - 72
YING ET AL., CELL, vol. 115, 2003, pages 281 - 292
YING ET AL., NATURE, vol. 453, 2008, pages 519 - 523
ZHOU ET AL., CELL STEM CELL, vol. 4, 2009, pages 1 - 4

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013159091A3 (fr) * 2012-04-20 2015-04-30 Aptamir Therapeutics, Inc. Modulateurs de microarn de la thermogenèse
US9034839B2 (en) 2012-04-20 2015-05-19 Aptamir Therapeutics, Inc. miRNA modulators of thermogenesis
US9453224B2 (en) 2012-04-20 2016-09-27 Aptamir Therapeutics, Inc. MiRNA modulators of thermogenesis
US9803203B2 (en) 2012-04-20 2017-10-31 Aptamir Therapeutics, Inc. MiRNA modulators of thermogenesis
US10253319B2 (en) 2012-04-20 2019-04-09 Aptamir Therapeutics, Inc. miRNA modulators of thermogenesis
WO2015104424A1 (fr) * 2014-01-13 2015-07-16 Centre Leon Berard Procede de preparation de cellules pluripotentes induites
FR3016372A1 (fr) * 2014-01-13 2015-07-17 Ct Leon Berard Procede de preparation de cellules pluripotentes induites
CN106459909A (zh) * 2014-01-13 2017-02-22 利昂贝拉尔中心 生产诱导多能细胞的方法
CN103877595A (zh) * 2014-03-21 2014-06-25 中国科学院生物物理研究所 人类免疫缺陷病毒抑制剂或药物增敏剂的筛选方法
US12286625B2 (en) 2016-04-29 2025-04-29 Aptamir Therapeutics, Inc. Inhibition of mir-22 miRNA by APT-110
KR102087084B1 (ko) * 2020-02-03 2020-03-10 주식회사 이에이치엘바이오 항노화인자를 발현하는 지방유래 줄기세포의 대량 배양방법
CN117904034A (zh) * 2024-01-19 2024-04-19 杏林医学科技(江苏)有限公司 自体干细胞培养液及其在修复女性生殖器官凝胶上的应用

Also Published As

Publication number Publication date
WO2012007725A3 (fr) 2012-03-08

Similar Documents

Publication Publication Date Title
US12180509B2 (en) Methods for reprograming non-pluripotent cells into pluripotent stem cells
JP6899792B2 (ja) 人工多能性幹細胞を作製するための化学的手法と遺伝的手法の組み合わせ法
Romito et al. Pluripotent stem cells: current understanding and future directions
CN110662832B (zh) 由间介中胚层细胞分化诱导肾祖细胞的方法和由多能干细胞分化诱导肾祖细胞的方法
WO2012007725A2 (fr) Procédé de reprogrammation d'une cellule
US20090252711A1 (en) Stem Cells And Methods Of Making And Using Stem Cells
US11725189B2 (en) Maintenance culture of induced pluripotent stem cell-derived intestinal stem cells
KR102446763B1 (ko) 다능성 줄기 세포로부터 장관 상피 세포로의 분화 유도 방법
JP2014520551A (ja) 細胞のリプログラミング方法およびゲノムの改変方法
WO2013086570A1 (fr) Procédé de production de cellules souches multipotentes
JP7307481B2 (ja) 始原生殖細胞／始原生殖細胞様細胞の維持増幅及び分化誘導方法
WO2012020687A1 (fr) Procédé d'induction de la différenciation en cellules germinales à partir de cellules souches pluripotentes
JP2011050379A (ja) イヌｉＰＳ細胞及びその製造方法
JP6351018B2 (ja) アミノ酸組成変更培地を用いた幹細胞の分化誘導方法、及び該培地を含む培地キット
WO2020213725A1 (fr) Procédé de production et kit de cellules souches pluripotentes induites
WO2010130446A1 (fr) Procédé de production de systèmes d'essai à partir de donneurs souffrant d'effets secondaires dus à des médicaments et/ou de traitements thérapeutiques, et utilisations desdits systèmes
JP2022019411A (ja) 人工多能性幹細胞由来の内胚葉細胞を製造する方法及びその利用
US20240358767A1 (en) Stem cell differentiation and chemical compounds
US11634686B2 (en) Method of producing naive pluripotent stem cells
JP7058330B2 (ja) 腸管上皮細胞の製造方法および腸管上皮細胞
WO2025018366A1 (fr) Procédé de production de cellules épithéliales intestinales
JPWO2020095879A1 (ja) 多能性幹細胞の腸管上皮細胞への分化誘導
Hongbao et al. The octamer-binding transcription factor 4 (Oct-4) and stem cell literatures

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: 11738768

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11738768

Country of ref document: EP

Kind code of ref document: A2

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