CA2959404A1 - Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss - Google Patents

Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss Download PDF

Info

Publication number
CA2959404A1
CA2959404A1 CA2959404A CA2959404A CA2959404A1 CA 2959404 A1 CA2959404 A1 CA 2959404A1 CA 2959404 A CA2959404 A CA 2959404A CA 2959404 A CA2959404 A CA 2959404A CA 2959404 A1 CA2959404 A1 CA 2959404A1
Authority
CA
Canada
Prior art keywords
cells
lgr5
differentiation
cell
inhibitor
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.)
Pending
Application number
CA2959404A
Other languages
English (en)
French (fr)
Inventor
Jeffrey M. Karp
Robert S. Langer
Xiaolei YIN
Nitin JOSHI
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.)
The Brigham and Women's Hospital Inc
Massachusetts Institute of Technology
Original Assignee
The Brigham and Women's Hospital Inc
Massachusetts Institute of Technology
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 The Brigham and Women's Hospital Inc, Massachusetts Institute of Technology filed Critical The Brigham and Women's Hospital Inc
Publication of CA2959404A1 publication Critical patent/CA2959404A1/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • 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
    • A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0046—Ear
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • 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
    • 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
    • C12N5/0618—Cells of the nervous system
    • C12N5/062—Sensory transducers, e.g. photoreceptors; Sensory neurons, e.g. for hearing, taste, smell, pH, touch, temperature, pain
    • 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
    • C12N5/0625—Epidermal cells, skin cells; Cells of the oral mucosa
    • C12N5/0627—Hair cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/38—Vitamins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/105—Insulin-like growth factors [IGF]
    • 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
    • C12N2501/11—Epidermal growth factor [EGF]
    • 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
    • C12N2501/10—Growth factors
    • C12N2501/15—Transforming growth factor beta (TGF-β)
    • 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
    • C12N2501/415—Wnt; Frizzeled
    • 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
    • C12N2501/42—Notch; Delta; Jagged; Serrate
    • 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
    • C12N2501/70—Enzymes
    • C12N2501/73—Hydrolases (EC 3.)
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Neurology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Dermatology (AREA)
  • Neurosurgery (AREA)
  • Analytical Chemistry (AREA)
  • Acoustics & Sound (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Pain & Pain Management (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
CA2959404A 2014-09-03 2015-09-03 Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss Pending CA2959404A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201462045506P 2014-09-03 2014-09-03
US62/045,506 2014-09-03
US201462051003P 2014-09-16 2014-09-16
US62/051,003 2014-09-16
PCT/US2015/048442 WO2016037016A1 (en) 2014-09-03 2015-09-03 Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss

Publications (1)

Publication Number Publication Date
CA2959404A1 true CA2959404A1 (en) 2016-03-10

Family

ID=54289054

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2959404A Pending CA2959404A1 (en) 2014-09-03 2015-09-03 Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss

Country Status (9)

Country Link
US (3) US10568883B2 (enExample)
EP (1) EP3189134A1 (enExample)
JP (3) JP6773645B2 (enExample)
KR (2) KR20230019500A (enExample)
CN (1) CN107073042A (enExample)
AU (1) AU2015311816B2 (enExample)
CA (1) CA2959404A1 (enExample)
IL (2) IL299964A (enExample)
WO (1) WO2016037016A1 (enExample)

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008076556A2 (en) 2006-11-15 2008-06-26 Massachusetts Eye & Ear Infirmary Generation of inner ear cells
BR112015023261A2 (pt) 2013-03-14 2017-07-18 Massachusetts Inst Technology composições e métodos para expansão e cultura de células-tronco epiteliais
WO2016022776A2 (en) 2014-08-06 2016-02-11 Massachusetts Eye And Ear Infirmary Increasing atoh1 life to drive sensorineural hair cell differentiantion
CN107073042A (zh) 2014-09-03 2017-08-18 布里格海姆妇女医院公司 用于产生内耳毛细胞来治疗听力损失的组合物、系统和方法
WO2017096233A1 (en) 2015-12-04 2017-06-08 Massachusetts Eye And Ear Infirmary Treatment of hearing loss by inhibition of casein kinase 1
CA3010610A1 (en) 2016-01-08 2017-07-13 The Brigham And Women's Hospital, Inc. Production of differentiated enteroendocrine cells and insulin producing cells
CN109219439B (zh) * 2016-01-29 2022-09-20 马萨诸塞眼科耳科诊所 内耳支持细胞的扩增和分化及其使用方法
US10213511B2 (en) 2016-03-02 2019-02-26 Frequency Therapeutics, Inc. Thermoreversible compositions for administration of therapeutic agents
US20170252339A1 (en) * 2016-03-02 2017-09-07 Frequency Therapeutics, Inc. Methods for controlled proliferation of stem cells / generating inner ear hair cells using 2-pyrimidinylaminoethylamino-2-pyridyl based compounds
US20190093079A1 (en) * 2016-03-02 2019-03-28 Frequency Therapeutics, Inc. Methods for controlled proliferation of stem cells / generating inner ear hair cells using gsk-3-alpha inhibitors
US11260130B2 (en) 2016-03-02 2022-03-01 Frequency Therapeutics, Inc. Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV
US20190060371A1 (en) * 2016-03-02 2019-02-28 Frequency Therapeutics, Inc. Methods for controlled proliferation of vestibular stem cells / generating inner ear hair cells using wnt and tgfbeta-inhibition
US10201540B2 (en) 2016-03-02 2019-02-12 Frequency Therapeutics, Inc. Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I
CN109562140B (zh) * 2016-06-03 2023-01-03 霍夫耳科研究所 用于内耳感觉毛细胞再生/替换的联合疗法
WO2018005284A1 (en) * 2016-06-27 2018-01-04 The United State Of America, As Represented By The Secretary, Department Of Health And Human Services Methods and compositions for influenza a virus subtyping
US10383881B2 (en) 2016-12-30 2019-08-20 Frequency Therapeutics, Inc. 1,5-dihydro-2H-pyrrol-2-one compounds and methods of using same
AU2017386417B2 (en) * 2016-12-30 2022-07-14 Frequency Therapeutics, Inc. 1H-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells
KR20190133703A (ko) * 2017-03-24 2019-12-03 노파르티스 아게 이속사졸 카르복사미드 화합물 및 이의 용도
JP2019007835A (ja) * 2017-06-23 2019-01-17 シャープ株式会社 測定方法、測定キットおよび測定装置
KR102484363B1 (ko) 2017-07-05 2023-01-03 삼성디스플레이 주식회사 박막 트랜지스터 표시판
CN111699003B (zh) 2017-12-19 2024-05-03 瑟罗泽恩奥普瑞汀公司 抗lrp5/6抗体和使用方法
CN118271444A (zh) 2017-12-19 2024-07-02 瑟罗泽恩奥普瑞汀公司 Wnt替代分子和其用途
JP7418332B2 (ja) 2017-12-19 2024-01-19 スロゼン オペレーティング， インコーポレイテッド 抗フリズルド抗体及び使用方法
US11590152B2 (en) 2018-01-26 2023-02-28 Massachusetts Eye And Ear Infirmary Treatment of hearing loss
CN108085296B (zh) * 2018-01-29 2021-04-13 清华大学 肠上皮类器官无生长因子培养方法
KR102071302B1 (ko) * 2018-06-28 2020-01-30 한국과학기술연구원 엑소좀 기반의 심근세포 교차분화 유도방법
EP3837350A1 (en) * 2018-08-17 2021-06-23 Frequency Therapeutics, Inc. Compositions and methods for generating hair cells by upregulating pi3k
WO2020037326A1 (en) 2018-08-17 2020-02-20 Frequency Therapeutics, Inc. Compositions and methods for generating hair cells by downregulating foxo
WO2020037323A1 (en) 2018-08-17 2020-02-20 Frequency Therapeutics, Inc. Compositions and methods for generating hair cells by upregulating jag-1
BR112021006092A2 (pt) * 2018-10-02 2021-07-20 Frequency Therapeutics, Inc. composições farmacêuticas que compreendem agentes terapêuticos óticos e métodos relacionados
KR102132914B1 (ko) 2018-12-05 2020-07-10 단국대학교 천안캠퍼스 산학협력단 광생체조절을 이용한 배아줄기세포의 귀 연계 조직으로의 분화 방법
CN114174496A (zh) * 2019-02-08 2022-03-11 频率医疗公司 用于通过抑制表观遗传靶标来产生毛细胞的组合物和方法
US20220175884A1 (en) * 2019-04-02 2022-06-09 Surrozen Operating, Inc. Modulation of wnt signaling in auditory disorders
KR102050223B1 (ko) * 2019-04-04 2019-11-29 포항공과대학교 산학협력단 배아줄기세포로부터 소장 오가노이드의 제조방법
US20230000923A1 (en) * 2019-09-20 2023-01-05 Korea Research Institute Of Bioscience And Biotechnology Production method for induced dopaminergic neuronal progenitors, using direct reprogramming
WO2021127275A1 (en) * 2019-12-17 2021-06-24 Otonony, Inc. Gsk-3 modulator otic formulations
JP7842690B2 (ja) 2020-02-19 2026-04-08 ナミ セラピューティクス， インコーポレイテッド がんの処置において有用なＴＦＧβアンタゴニストプロドラッグを含有する製剤化および／または共製剤化リポソーム組成物ならびにその方法
KR102326582B1 (ko) * 2020-05-15 2021-11-16 사회복지법인 삼성생명공익재단 청각장애의 진단용 마커 및 그의 용도
KR102315584B1 (ko) * 2020-05-29 2021-10-21 단국대학교 천안캠퍼스 산학협력단 청각 내이 내 lgr5+ 청각 전구세포 분리방법
WO2022164788A2 (en) * 2021-01-26 2022-08-04 The Trustees Of Indiana University Pharmaceutical compositions and their methods of use
WO2022164786A1 (en) * 2021-01-26 2022-08-04 The Trustees Of Indiana University Pharmaceutical compositions and their methods of use
CN112870383A (zh) * 2021-02-20 2021-06-01 东南大学 Hippo调控内耳干细胞增殖分化方法及在毛细胞再生中的应用
CN118946660A (zh) * 2021-12-09 2024-11-12 印第安纳大学托管会 生成人耳蜗毛细胞的方法

Family Cites Families (123)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5059591B1 (en) 1983-05-26 2000-04-25 Liposome Co Inc Drug preparations of reduced toxicity
US5571714A (en) 1988-12-22 1996-11-05 Celtrix Pharmaceuticals, Inc. Monoclonal antibodies which bind both transforming growth factors β1 and β2 and methods of use
US6124449A (en) 1990-06-11 2000-09-26 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US5731144A (en) 1990-06-11 1998-03-24 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands
US5731424A (en) 1990-06-11 1998-03-24 Nexstar Pharmaceuticals, Inc. High affinity TGFβ nucleic acid ligands and inhibitors
US5561163A (en) 1990-08-31 1996-10-01 Deprenyl Animal Health, Inc. Treating hearing loss with deprenyl
US5421818A (en) 1993-10-18 1995-06-06 Inner Ear Medical Delivery Systems, Inc. Multi-functional inner ear treatment and diagnostic system
GB9601081D0 (en) 1995-10-06 1996-03-20 Cambridge Antibody Tech Specific binding members for human transforming growth factor beta;materials and methods
US5837681A (en) 1996-02-23 1998-11-17 Amgen Inc. Method for treating sensorineural hearing loss using glial cell line-derived neurotrophic factor (GDNF) protein product
US6593290B1 (en) 1996-11-01 2003-07-15 Genentech, Inc. Treatment of inner ear hair cells
US6045528A (en) 1997-06-13 2000-04-04 Intraear, Inc. Inner ear fluid transfer and diagnostic system
US6806358B1 (en) 1997-12-16 2004-10-19 University Of California San Diego Peptide inhibitor of TGF-β growth factors
US6177434B1 (en) 1997-12-16 2001-01-23 The United States Of America As Represented By The Secretary Of The Navy Prevention or reversal of sensorineural hearing loss (SNHL) through biologic mechanisms
AU760046B2 (en) 1998-02-27 2003-05-08 United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs
GB9809869D0 (en) 1998-05-09 1998-07-08 Medical Res Council Inhibition of protein kinases
US6184226B1 (en) 1998-08-28 2001-02-06 Scios Inc. Quinazoline derivatives as inhibitors of P-38 α
ES2146552B1 (es) 1998-11-24 2001-04-16 Inst Cientifico Tecnol Navarra Peptidos inhibidores de tgf/31
AU4206200A (en) 1999-04-05 2000-10-23 Adherex Technologies Inc. Compounds and methods for stimulating beta-catenin mediated gene expression and differentiation
US6492497B1 (en) 1999-04-30 2002-12-10 Cambridge Antibody Technology Limited Specific binding members for TGFbeta1
DE60129222T2 (de) 2000-05-11 2008-03-06 Consejo Superior de Investigaciónes Científicas Heterocyclischen inhibitoren von glycogen synthase kinase gsk-3
US6509318B1 (en) 2000-09-29 2003-01-21 The Regents Of The University Of California TGF-B inhibitors and methods
US20050287128A1 (en) 2001-05-18 2005-12-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA)
US20050227936A1 (en) 2001-05-18 2005-10-13 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA)
SI1397364T1 (sl) 2001-05-24 2007-12-31 Lilly Co Eli Novi pirolni derivati kot farmacevtske uäśinkovine
US20030028905A1 (en) 2001-07-31 2003-02-06 Petra Knaus Mutant forms of the TGF-beta type II receptor which bind all TGF-beta isoforms
IL161662A0 (en) 2001-11-01 2004-09-27 Janssen Pharmaceutica Nv Heteroaryl amines as glycogen synthase kinase 3 beta inhibitors (gsk3 inhibitors)
SE0200979D0 (sv) 2002-03-28 2002-03-28 Astrazeneca Ab New compounds
US20040006030A1 (en) 2002-07-02 2004-01-08 Isis Pharmaceuticals Inc. Antisense modulation of TGF-beta 2 expression
JP2005530800A (ja) 2002-05-15 2005-10-13 スミスクライン・ビーチャム・コーポレイション ベンゾオキサジンおよびベンゾオキサジノン置換トリアゾール
AU2003229305A1 (en) 2002-05-17 2003-12-02 Scios, Inc. TREATMENT OF FIBROPROLIFERATIVE DISORDERS USING TGF-Beta INHIBITORS
US7190468B2 (en) 2002-07-17 2007-03-13 Hewlett-Packard Development Company, L.P. Background document rendering system and method
EP1539748A1 (en) 2002-07-31 2005-06-15 Smithkline Beecham Corporation 2-phenylpyridin-4-yl derivatives as alk5 inhibitors
EP1739087A1 (en) 2002-08-02 2007-01-03 Vertex Pharmaceuticals Incorporated Pyrazole compositions useful as inhibitors of gsk-3
MXPA05001367A (es) 2002-08-02 2005-04-28 Vertex Pharma Composiciones de pirazol utiles como inhibidores de gsk-3.
UA80296C2 (en) 2002-09-06 2007-09-10 Biogen Inc Imidazolopyridines and methods of making and using the same
WO2004026871A1 (en) 2002-09-17 2004-04-01 Eli Lilly And Company Novel pyrazolopyridine derivatves as pharmaceutical agents
KR20050057441A (ko) 2002-09-18 2005-06-16 화이자 프로덕츠 인코포레이티드 전환 성장 인자 억제제로서의 신규한 아이소티아졸 및아이속사졸 화합물
JP2006502236A (ja) 2002-09-18 2006-01-19 ファイザー・プロダクツ・インク 形質転換成長因子（ｔｇｆ）阻害剤としてのトリアゾール誘導体
WO2004047818A2 (en) 2002-11-22 2004-06-10 Scios, Inc. USE OF TFG-β INHIBITORSTO COUNTERACT PATHOLOGIC CHANGES IN THE LEVEL OR FUNCTION OF STEROID/THYROID RECEPTORS
JP2006516603A (ja) 2003-01-27 2006-07-06 ファイザー・プロダクツ・インク イソチアゾール誘導体
DE602004014347D1 (de) 2003-03-12 2008-07-24 Millennium Pharm Inc Chinazolin-derivate als tgf-beta-inhibitoren
EP1608631A4 (en) 2003-03-28 2008-08-20 Scios Inc BICYCLIC PYRIMIDININHIBITORS OF TGF BETA
ES2389258T3 (es) 2003-06-17 2012-10-24 Millennium Pharmaceuticals, Inc. Composiciones y métodos para inhibir TGF-s
WO2005009287A2 (en) 2003-07-21 2005-02-03 University Of Maryland, Baltimore Drug delivery to the inner ear and methods of using same
SG145713A1 (en) 2003-08-13 2008-09-29 Univ Illinois SILENCING OF TGFss TYPE II RECEPTOR EXPRESSION BY SIRNA
JP4688680B2 (ja) 2003-10-28 2011-05-25 独立行政法人理化学研究所 ＴＧＦ−β情報伝達経路阻害剤
US8673634B2 (en) 2003-11-13 2014-03-18 Massachusetts Eye & Ear Infirmary Method for the treatment of hearing loss
GB0327908D0 (en) 2003-12-02 2004-01-07 Neuropharma Sa GSK-3 inhibitors isolated from marine organisms
CA2551524A1 (en) 2003-12-24 2005-07-21 Scios, Inc. Treatment of malignant gliomas with tgf-beta inhibitors
US7368445B2 (en) 2004-03-01 2008-05-06 Eli Lilly And Company Fused pyrazole derivatives as TGF-β signal transduction inhibitors for the treatment of fibrosis and neoplasms
AR048335A1 (es) 2004-03-24 2006-04-19 Chugai Pharmaceutical Co Ltd Agentes terapeuticos para trastornos del oido interno que contienen un antagonista de il- 6 como un ingrediente activo
WO2005115527A2 (en) 2004-05-24 2005-12-08 Auris Medical, Llc. Combined otic aspirator and medication dispenser
GB0418328D0 (en) 2004-08-17 2004-09-22 Imp College Innovations Ltd Cancer methods and medicaments
JP2007176795A (ja) 2004-08-18 2007-07-12 Univ Nihon ＴＧＦ−β遺伝子発現抑制剤
WO2006034207A2 (en) 2004-09-17 2006-03-30 Vanderbilt University Use of gsk3 inhibitors in combination with radiation therapies
CA2597098C (en) 2005-02-08 2016-08-02 Steven R. Ledbetter Antibodies to tgfbeta
GB0505970D0 (en) 2005-03-23 2005-04-27 Univ Edinburgh Culture medium containing kinase inhibitor, and uses thereof
CN101189234B (zh) 2005-03-25 2011-08-17 泰博特克药品有限公司 Hcv的杂二环抑制剂
DK1864132T3 (da) 2005-03-31 2012-07-16 Stemnion Inc Fra amnion stammende cellesammensætninger, fremgangsmåder til fremstilling deraf og anvendelser deraf
UA92608C2 (en) 2005-06-30 2010-11-25 Янссен Фармацевтика Н.В. Cyclic anilino - pyridinotriazines as gsk-3 inhibitors
CA2616196C (en) 2005-07-22 2012-08-21 Eli Lilly And Company A pyridin quinolin substituted pyrrolo [1,2-b] pyrazole monohydrate as tgf-beta inhibitor
EP1749523A1 (en) 2005-07-29 2007-02-07 Neuropharma, S.A. GSK-3 inhibitors
CA2625883A1 (en) 2005-10-14 2007-04-26 Regents Of The University Of Minnesota Differentiation of non-embryonic stem cells to cells having a pancreatic phenotype
AU2005337776B2 (en) 2005-10-24 2013-01-31 Proyecto De Biomedicina Cima, S.L. Use of TGF-Beta1 inhibitor peptides in the preparation of an immune response modulating agent
US7951845B2 (en) 2006-01-19 2011-05-31 The Regents Of The University Of Michigan Composition and method of treating hearing loss
ITMI20060181A1 (it) 2006-02-03 2007-08-04 Univ Padova Modulatori del tgf-b e loro uso
TW200800203A (en) 2006-03-08 2008-01-01 Astrazeneca Ab New use
WO2007109097A2 (en) 2006-03-16 2007-09-27 Alnylam Pharmaceuticals, Inc. RNAi MODULATION OF TGF-BETA AND THERAPEUTIC USES THEREOF
ES2725601T3 (es) 2006-04-28 2019-09-25 Lifescan Inc Diferenciación de células madre embriónicas humanas
CA2661334C (en) 2006-08-23 2011-11-29 Pfizer Products Inc. Pyrimidone compounds as gsk-3 inhibitors
WO2008076556A2 (en) 2006-11-15 2008-06-26 Massachusetts Eye & Ear Infirmary Generation of inner ear cells
CA2673368C (en) 2006-12-19 2014-10-28 The Board Of Trustees Of The University Of Illinois 3-benzofuranyl-4-indolyl maleimides as potent gsk3 inhibitors for neurogenerative disorders
WO2009017453A1 (en) 2007-07-30 2009-02-05 Astrazeneca Ab New therapeutic combination of an antipsychotic and a gsk3 inhibitor 958
WO2009017455A1 (en) 2007-07-30 2009-02-05 Astrazeneca Ab A new combination of (a) an alpha-4-beta-2 -neuronal nicotinic agonist and (b) a gsk3 inhibitor
EP2197876A1 (en) 2007-08-29 2010-06-23 Glaxosmithkline LLC Thiazole and oxazole kinase inhibitors
US8377886B2 (en) 2007-09-14 2013-02-19 Albert Einstein College Of Medicine Of Yeshiva University Use of gamma secretase inhibitors and notch pathway inhibitors for treatment and prevention of renal disease
JP5951254B2 (ja) * 2008-03-17 2016-07-13 ザ スクリプス リサーチ インスティテュート 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
WO2009132050A2 (en) 2008-04-21 2009-10-29 Otonomy, Inc. Auris formulations for treating otic diseases and conditions
US20090270497A1 (en) 2008-04-24 2009-10-29 Pharmacyclics, Inc. Treatment of Non-Localized Inflammation with pan-HDAC Inhibitors
WO2009142719A2 (en) 2008-05-19 2009-11-26 Massachusetts Institute Of Technology Tympanic membrane permeating ear drops and uses thereof
WO2010011466A2 (en) 2008-06-27 2010-01-28 Otonomy, Inc. Controlled-release cns modulating compositions and methods for the treatment of otic disorders
US8496957B2 (en) 2008-07-21 2013-07-30 Otonomy, Inc Controlled release auris sensory cell modulator compositions and methods for the treatment of otic disorders
US8298825B1 (en) 2008-08-25 2012-10-30 The General Hospital Corporation TGF-beta receptor inhibitors to enhance direct reprogramming
US20120059021A1 (en) * 2008-11-11 2012-03-08 University Of Washington Compositions and methods for treating cancer and methods for predicting a response to such treatments
WO2010060088A2 (en) * 2008-11-24 2010-05-27 Massachusetts Eye & Ear Infirmary Pathways to generate hair cells
EP2376626A4 (en) 2008-12-13 2012-10-17 Dna Microarray MICRO-ENVIRONMENTAL NICHE ASSAY FOR SCREENING OF INDUCED PLURIPOTENT STEM CELLS (CIPS)
US20130039998A1 (en) 2008-12-24 2013-02-14 University Of Washington Compositions of modulators of the wnt/beta-catenin pathway and benzamide and/or hydroxamic acid derivatives to treat bipolar disorder
US8642339B2 (en) 2009-02-03 2014-02-04 Koninklijke Nederlandse Akademie Van Wetenschappen Culture medium for epithelial stem cells and organoids comprising the stem cells
GB201111244D0 (en) 2011-06-30 2011-08-17 Konink Nl Akademie Van Wetenschappen Knaw Culture media for stem cells
US9752124B2 (en) 2009-02-03 2017-09-05 Koninklijke Nederlandse Akademie Van Wetenschappen Culture medium for epithelial stem cells and organoids comprising the stem cells
EP2412800A1 (en) * 2010-07-29 2012-02-01 Koninklijke Nederlandse Akademie van Wetenschappen Liver organoid, uses thereof and culture method for obtaining them
CA2755120C (en) 2009-03-11 2017-05-16 Kyorin Pharmaceutical Co., Ltd. 7-cycloalkylaminoquinolones as gsk-3 inhibitors
WO2011019957A1 (en) 2009-08-12 2011-02-17 University Of Southern California Method for formation of induced pluripotent stem cells
LT2494039T (lt) 2009-10-31 2019-07-25 Genesis Technologies Limited Ląstelių perprogramavimo būdai ir jų panaudojimas
US20110135756A1 (en) 2009-12-08 2011-06-09 University Of Washington Compositions and methods for protecting sensory hair cells
CA2785233C (en) 2009-12-28 2018-10-09 Audiocure Pharma Gmbh .beta.-carbolines for treatment of hearing damages and vertigo
US8198285B2 (en) 2010-01-19 2012-06-12 Astrazeneca Ab Pyrazine derivatives
WO2011116930A1 (en) 2010-03-22 2011-09-29 Cellartis Ab Directed differentiation and maturation of pluripotent cells into hepatocyte like cells by modulation of wnt-signalling pathway
CA2800498C (en) 2010-03-31 2021-11-16 The Scripps Research Institute Reprogramming cells
ES2705236T3 (es) 2010-05-12 2019-03-22 Univ Columbia Procedimientos para producir células enteroendocrinas que producen y secretan insulina
CN103459591B (zh) 2010-11-02 2016-05-04 国立大学法人熊本大学 肠细胞的制造方法
EP2667881A4 (en) 2011-01-24 2015-04-22 Univ Leland Stanford Junior METHOD FOR IN VITRO GENERATION OF INTERNAL CELLS
KR101807704B1 (ko) 2011-04-12 2017-12-13 차의과학대학교 산학협력단 역분화-증진제를 이용한 역분화 만능 줄기세포의 제조방법
HUE041576T2 (hu) * 2011-09-14 2019-05-28 Samumed Llc Indazol-3-karboxamid-származékok és alkalmazásuk Wnt/b-katenin szignalizáló útvonal inhibitorokként
EP2765188B1 (en) 2011-10-06 2017-12-06 Keio University Method for producing corneal endothelial cell
EP2838888B1 (en) 2012-02-24 2017-04-12 ASD Therapeutics Partners LLC Thiadiazolidinediones as gsk-3 inhibitors
US9457009B2 (en) 2012-05-31 2016-10-04 The United States Of America As Represented By The Department Of Veterans Affairs Methods and compositions for preventing and treating auditory dysfunctions
TW201406758A (zh) 2012-06-28 2014-02-16 Daiichi Sankyo Co Ltd 三環性化合物
GB201212960D0 (en) 2012-07-20 2012-09-05 Common Services Agency Erythroid production
CA2884309A1 (en) * 2012-09-07 2014-03-13 Massachusetts Eye And Ear Infirmary Methods and compositions for regenerating hair cells and/or supporting cells from differentiated cochlear cells or differentiated utricular cells by modulation of notch and cmyc activity
WO2014050779A1 (ja) 2012-09-25 2014-04-03 第一三共株式会社 Ｇｓｋ３阻害剤と抗ｄｒ５抗体の組み合わせ
DK2909204T3 (en) 2012-10-12 2019-04-01 Broad Inst Inc GSK3 INHIBITORS AND METHODS FOR USE THEREOF
CN105143445B (zh) 2012-11-29 2020-07-07 宝生物欧洲公司 衍生自人多能干细胞的肝细胞样细胞的成熟
US20140248696A1 (en) 2013-03-01 2014-09-04 Wisconsin Alumni Research Foundation Methods of maintaining, expanding, and diffrentiating neuronal subtype specific progenitors
BR112015023261A2 (pt) 2013-03-14 2017-07-18 Massachusetts Inst Technology composições e métodos para expansão e cultura de células-tronco epiteliais
WO2015168149A2 (en) * 2014-04-28 2015-11-05 Massachusetts Eye & Ear Infirmary Sensorineural hair cell differentiation
US10457915B2 (en) 2014-05-15 2019-10-29 International Stem Cell Corporation Chemical differentiation of pluripotentstem cells into retinal epithelial cells
CN107073042A (zh) 2014-09-03 2017-08-18 布里格海姆妇女医院公司 用于产生内耳毛细胞来治疗听力损失的组合物、系统和方法
CN104726395B (zh) 2015-03-20 2018-03-23 深圳市人民医院 一种诱导人诱导多能干细胞定向分化为胰腺细胞的方法
GB201505605D0 (en) 2015-03-31 2015-05-13 Univ Sheffield Method for producing otic progenitors
EP3350313B1 (en) 2015-09-15 2025-11-26 Agency For Science, Technology And Research (A*star) Derivation of liver organoids from human pluripotent stem cells
CA3010610A1 (en) 2016-01-08 2017-07-13 The Brigham And Women's Hospital, Inc. Production of differentiated enteroendocrine cells and insulin producing cells
WO2019183572A1 (en) 2018-03-23 2019-09-26 Refuge Biotechnologies, Inc. Gene regulation via conditional nuclear localization of gene modulating polypeptides

Also Published As

Publication number Publication date
US20190247395A9 (en) 2019-08-15
KR20170055497A (ko) 2017-05-19
IL250652A0 (en) 2017-04-30
US11369607B2 (en) 2022-06-28
JP6773645B2 (ja) 2020-10-21
US20200323853A1 (en) 2020-10-15
EP3189134A1 (en) 2017-07-12
AU2015311816A1 (en) 2017-04-20
CN107073042A (zh) 2017-08-18
AU2015311816B2 (en) 2019-04-04
KR20230019500A (ko) 2023-02-08
US20220339154A1 (en) 2022-10-27
IL250652B2 (en) 2023-06-01
JP2017527285A (ja) 2017-09-21
JP2020178716A (ja) 2020-11-05
IL299964A (en) 2023-03-01
WO2016037016A1 (en) 2016-03-10
JP2023002795A (ja) 2023-01-10
US20170071937A1 (en) 2017-03-16
US10568883B2 (en) 2020-02-25
KR102493376B1 (ko) 2023-01-27
JP7237044B2 (ja) 2023-03-10

Similar Documents

Publication Publication Date Title
US20220339154A1 (en) Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss
US20190093079A1 (en) Methods for controlled proliferation of stem cells / generating inner ear hair cells using gsk-3-alpha inhibitors
US11162071B2 (en) Compositions and methods for generating hair cells by upregulating JAG-1
US10016507B2 (en) Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: III
US11033546B2 (en) Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: I
US20190060371A1 (en) Methods for controlled proliferation of vestibular stem cells / generating inner ear hair cells using wnt and tgfbeta-inhibition
US20220160664A1 (en) Taz activators and wnt agonists for treating ear disorders
US20220008433A1 (en) Inhibition of Lysine Demethylase 1 (Lsd1) Induces Differentiation of Hair Cells
US20220127568A1 (en) Compositions and methods for generating hair cells by inhibiting epigenetic targets
US20200080055A1 (en) Compositions and methods for generating hair cells by upregulating pi3k
US11260130B2 (en) Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV
HK1238175A1 (en) Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss
US20170252329A1 (en) Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using gsk3 inhibitors: ii

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20200828