公开(公告)号：US20230390459A1

公开(公告)日：2023-12-07

申请号：US18034645

申请日：2021-10-28

申请人： KEIO UNIVERSITY ,  Jiksak Bioengineering Inc.

发明人： Shinsuke SHIBATA ,  Hiroo KIMURA ,  Takayuki NISHIJIMA ,  Tomoko SHINDO ,  Hideyuki OKANO ,  Jiro KAWADA ,  Sayaka TOITA

IPC分类号： A61L27/38

CPC分类号： A61L27/3878 ,  A61L27/3895 ,  A61L27/383

摘要： The present invention relates to an axon bundle obtained by a method of culturing a nerve cell aggregation having one spheroid and an axon bundle extending from the spheroid



wherein the nerve cell aggregation consisting of a plurality of neurons having a cell body and an axon obtained by a method comprising the following step:
supplying a culture medium to one first chamber, one second chamber and one channel having the length of at least 1 mm, the width of 100 to 150 μm and the height of 100 to 200 μm, which connecting said first chamber and second chamber, wherein said first chamber, second chamber, and channel are contained in one of the modules disposed in a culture plate,
seeding the first chamber with a nerve cell derived from a stem cell or a spheroid of primary cultured nerve cells; and
culturing said nerve cell, thereby growing an axon bundle from said spheroid and extending them into said channel,
wherein the length of the axon bundle obtained is 1 mm or more, and the diameter of the axon bundles is 50 μm or more.

公开(公告)号：US20230203439A1

公开(公告)日：2023-06-29

申请号：US18116415

申请日：2023-03-02

申请人： JSR Corporation ,  KEIO UNIVERSITY

发明人： Mitsuru ISHIKAWA ,  Hideyuki OKANO

IPC分类号： C12N5/079 ,  C12N15/86

CPC分类号： C12N5/0622 ,  C12N15/86 ,  C12N2501/60 ,  C12N2506/45 ,  C12N2740/15043

摘要： A method is provided for producing oligodendrocyte-like cells, including (A) increasing abundances of oligodendrocyte transcription factor 2 (OLIG2) mutant and SRY-box transcription factor 10 (SOX10) in human pluripotent stein cells and (B) culturing the human pluripotent stem cells in which the abundances of the OLIG2 mutant and the SOX10 are increased and consequently differentiating the human pluripotent stem cells into oligodendrocyte-like cells, in which the OLIG2 mutant lacks a serine residue of wild-type OLIG2 at position 147, or the serine residue of the wild-type OLIG2 at position 147 is substituted with an amino acid other than serine.

公开(公告)号：US20180080009A1

公开(公告)日：2018-03-22

申请号：US15558473

申请日：2016-03-17

申请人： ONO PHARMACEUTICAL CO., LTD. ,  KEIO UNIVERSITY

发明人： Hideyuki OKANO ,  Seiji SHIOZAWA ,  Fumihiko KISA

IPC分类号： C12N5/074

CPC分类号： C12N5/0696 ,  C12N5/10 ,  C12N15/09 ,  C12N2501/01 ,  C12N2501/20 ,  C12N2501/60 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/605 ,  C12N2501/606

摘要： To produce and/or maintain naïve pluripotent stem cells capable of highly expressing genes important for maintaining an undifferentiated state, which could not be achieved by known methods for producing pluripotent stem cells. The present invention can produce naïve pluripotent stem cells capable of maintaining an undifferentiated state by introducing and allowing transient expression of six genes (Oct3/4, Klf4, c-Myc, Sox2, Nanog, and Klf2) among the so-called initializing factors, and further performing culturing in a medium containing LIF, an MEK inhibitor, a GSK3 inhibitor, a cAMP production promoter, a TGF-β inhibitor and a PKC inhibitor. Thus, the problem of the present invention can be solved.

公开(公告)号：US20240279605A1

公开(公告)日：2024-08-22

申请号：US18648566

申请日：2024-04-29

申请人： JSR CORPORATION ,  KEIO UNIVERSITY

发明人： Hayato HIRAMINE ,  Ryosuke NAGASHIMA ,  Sumihiro MAEDA ,  Hideyuki OKANO ,  Mitsuru ISHIKAWA

IPC分类号： C12N5/0793

CPC分类号： C12N5/0619 ,  C12N2500/36 ,  C12N2501/13 ,  C12N2513/00

摘要： A culture method includes culturing a spheroid of a human neural cell-like cell in the presence of a tau protein aggregate and culturing a culture product in a culture medium containing 5 μg/mL or greater of a lipid, in which the lipid is one or more selected from the group consisting of a glycerolipid, a glycerophospholipid, and a sphingolipid. The culture method includes culturing a spheroid of a human neural cell-like cell in the presence of a tau protein aggregate and culturing a culture product in a culture medium containing a neurotrophic factor.

公开(公告)号：US20240252546A1

公开(公告)日：2024-08-01

申请号：US18561077

申请日：2022-05-27

申请人： KEIO UNIVERSITY

发明人： Hideyuki OKANO ,  Yoshitaka KASE

IPC分类号： A61K35/30 ,  C12N5/0793 ,  G01N33/50

CPC分类号： A61K35/30 ,  C12N5/0619 ,  G01N33/5058 ,  C12N2501/734 ,  C12N2503/00 ,  C12N2506/45

摘要： A neurite outgrowth promotion kit containing a γ-secretase inhibitor or a GADD45G expression vector, in which the neurite outgrowth promotion kit is used for significantly promoting neurite outgrowth of nerve cells as compared with a control, by acting on a neurosphere to induce differentiation of the neurosphere into nerve cells; a method for producing a neurosphere for treatment of spinal cord injury, which includes a step of using the above-described neurite outgrowth promotion kit on a neurosphere derived from a pluripotent stem cell; a neurosphere for treatment of spinal cord injury; and a method for selecting a neurosphere for treatment of spinal cord injury and a method for screening a neurite outgrowth-promoting agent.

公开(公告)号：US20220326225A1

公开(公告)日：2022-10-13

申请号：US17709903

申请日：2022-03-31

申请人： FUJIFILM Corporation ,  KEIO UNIVERSITY

发明人： Hirokazu TANABE ,  Setsu ENDOH ,  Hitoshi MASUYAMA ,  Euikyung SHIN ,  Koichi SAITO ,  Hideyuki OKANO ,  Sumihiro MAEDA

IPC分类号： G01N33/50 ,  C12Q1/6897 ,  C12N5/0793 ,  C12N15/62 ,  C12N15/11 ,  C12N9/22 ,  C12N15/86 ,  C07K14/47

摘要： Objects to be achieved are to provide a nerve cell with which it is possible to visualize and quantify the intracellular tau without using the exogenous promoter and to provide a pluripotent stem cell with which the nerve cell can be produced, to provide a method of screening a substance, including using the pluripotent stem cell or nerve cell described above, and a substance screened by the above method, and to provide a kit including a targeting vector and a gRNA.
There is provided a pluripotent stem cell including a DNA encoding a reporter molecule, the DNA being introduced adjacent to an endogenous tau gene such that a tau protein is expressed as a fusion protein fused with a reporter molecule.

公开(公告)号：US20200325453A1

公开(公告)日：2020-10-15

申请号：US16917464

申请日：2020-06-30

申请人： ONO PHARMACEUTICAL CO., LTD. ,  KEIO UNIVERSITY

发明人： Hideyuki OKANO ,  Seiji Shiozawa ,  Fumihiko Kisa

IPC分类号： C12N5/074 ,  C12N5/10 ,  C12N15/09

摘要： To produce and/or maintain naïve pluripotent stem cells capable of highly expressing genes important for maintaining an undifferentiated state, which could not be achieved by known methods for producing pluripotent stem cells. The present invention can produce naïve pluripotent stem cells capable of maintaining an undifferentiated state by introducing and allowing transient expression of six genes (Oct3/4, Klf4, c-Myc, Sox2, Nanog, and Klf2) among the so-called initializing factors, and further performing culturing in a medium containing LIF, an MEK inhibitor, a GSK3 inhibitor, a cAMP production promoter, a TGF-β inhibitor and a PKC inhibitor. Thus, the problem of the present invention can be solved.

公开(公告)号：US20200299643A1

公开(公告)日：2020-09-24

申请号：US16086206

申请日：2017-03-27

申请人： KEIO UNIVERSITY

发明人： Hideyuki OKANO ,  Wado AKAMATSU ,  Koki FUJIMORI ,  Takuya MATSUMOTO ,  Naoko KUZUMAKI ,  Fumihiko KISA

IPC分类号： C12N5/0797 ,  C12N5/10

摘要： A culture medium for inducing a pluripotent stem cell into a differentiation-promoted pluripotent stem cell, the medium including a Glycogen synthase kinase 3β (GSK3β) inhibitor, a Bone morphogenic protein (BMP) signaling inhibitor, and a Transforming growth factor (TGF)-β inhibitor as active ingredients.

公开(公告)号：US20170340586A1

公开(公告)日：2017-11-30

申请号：US15544419

申请日：2016-01-13

申请人： Keio University

发明人： Makoto HOSOYA ,  Masato FUJIOKA ,  Hideyuki OKANO ,  Kaoru OGAWA ,  Tatsuo MATSUNAGA

IPC分类号： A61K31/155 ,  G01N33/50 ,  A61K31/439

CPC分类号： A61K31/436 ,  A61K31/155 ,  A61K31/439 ,  A61P27/16 ,  G01N33/5044 ,  G01N2510/00

摘要： An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided: wherein R1 to R7 are each independently selected from a hydrogen atom, a halogen atom, or a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkoxy carbonyl group, a C3-8 cycloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, and a phenyl group; wherein R1 is a C1-6 alkyl or a C3-6 alkynyl, R2 is H, —CH2-OH or —CH2—CH2OH, and X is ═O, (H, H) or (H, OH).

公开(公告)号：US20220380725A1

公开(公告)日：2022-12-01

申请号：US17773784

申请日：2020-11-05

申请人： JSR Corporation ,  KEIO UNIVERSITY

发明人： Hayato HIRAMINE ,  Hideyuki OKANO ,  Seiji SHIOZAWA ,  Mitsuru ISHIKAWA

IPC分类号： C12N5/079 ,  G01N33/50

摘要： According to a production method for a brain organoid, comprising a step 1 of carrying out suspension culture of human pluripotent stem cells having a mutation in at least one or more base sequences in an exon selected from the group consisting of an exon 9, an exon 10, an exon 11, an exon 12, and an exon 13 of a microtubule-associated protein tau (MAPT) gene, and having a mutation in at least one or more base sequences in an intron 10 of the MAPT gene, it is possible to produce a brain organoid having a phosphorylated 3-repeat tau protein and a phosphorylated 4-repeat tau protein.