AU2021247879B2 - Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent - Google Patents

Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent Download PDF

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AU2021247879B2
AU2021247879B2 AU2021247879A AU2021247879A AU2021247879B2 AU 2021247879 B2 AU2021247879 B2 AU 2021247879B2 AU 2021247879 A AU2021247879 A AU 2021247879A AU 2021247879 A AU2021247879 A AU 2021247879A AU 2021247879 B2 AU2021247879 B2 AU 2021247879B2
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cells
culture
mesenchymal stem
stem cells
laminin
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AU2021247879A1 (en
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Takefumi Ishidao
Itsunari Minami
Chugo RINOIE
Yasutomo YANAGITA
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Cell Exosome Therapeutics Inc
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Cell Exosome Therapeutics Inc
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    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662Stem cells
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    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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AU2021247879A 2020-03-31 2021-03-26 Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent Active AU2021247879B2 (en)

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AU2022259729A AU2022259729B2 (en) 2020-03-31 2022-10-25 Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent

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JP2020063408 2020-03-31
JP2020-063408 2020-03-31
PCT/JP2021/013099 WO2021200744A1 (ja) 2020-03-31 2021-03-26 増殖細胞の生産方法、細胞生産物の生産方法、間葉系幹細胞集団およびその生産方法、幹細胞の培養上清およびその生産方法、並びに治療剤

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AU2022259729A Active AU2022259729B2 (en) 2020-03-31 2022-10-25 Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent

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US (1) US20230172992A1 (https=)
EP (2) EP4130240A4 (https=)
JP (3) JPWO2021200744A1 (https=)
CN (2) CN115362252A (https=)
AU (2) AU2021247879B2 (https=)
CA (2) CA3177567A1 (https=)
TW (2) TW202204605A (https=)
WO (1) WO2021200744A1 (https=)

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JPWO2021200744A1 (https=) * 2020-03-31 2021-10-07
EP4324914B1 (en) * 2021-06-11 2026-03-18 Fullstem Co., Ltd. Exosome production promoting agent and exosome production promoting method
JP7763475B2 (ja) * 2021-12-24 2025-11-04 株式会社日本バイオセラピー研究所 培養上清を生産する方法
WO2024019080A1 (ja) * 2022-07-19 2024-01-25 国立大学法人 長崎大学 血管内皮増殖因子を高発現する臍帯由来間葉系細胞の製造方法、および肺疾患治療用医薬組成物
JP7851648B2 (ja) * 2022-12-23 2026-04-27 Cell Exosome Therapeutics株式会社 間葉系幹細胞又はその培養上清の利用
WO2025151805A1 (en) * 2024-01-10 2025-07-17 Biotech Therapeutics, LLC Mesenchymal stromal cell-derived extracellular vesicle-exosomes

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3009502A1 (en) * 2013-06-12 2016-04-20 Osaka University Cell culture equipment coated with laminin fragments in dry state
EP3170892A1 (en) * 2014-07-16 2017-05-24 Osaka University Method for enhancing activity of laminin fragment cell culture substrate

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5378612A (en) * 1990-05-11 1995-01-03 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Culture medium for production of recombinant protein
JPH05207875A (ja) * 1992-01-28 1993-08-20 Mitsui Toatsu Chem Inc 無血清培地
AU680909B2 (en) * 1994-04-06 1997-08-14 Immunex Corporation Interleukin-15
JPH10179147A (ja) * 1996-12-27 1998-07-07 Ishikawajima Harima Heavy Ind Co Ltd 植物細胞培養方法および二次代謝物高生産性植物細胞
EP1930413B1 (en) * 2005-08-23 2011-01-12 Oriental Yeast Co., Ltd. Technique for culture of mesenchymal stem cell utilizing laminin-5
AU2007294731B2 (en) * 2006-09-13 2014-04-17 Abbvie Inc. Cell culture improvements
WO2010040262A1 (zh) * 2008-10-10 2010-04-15 深圳市嘉天源生物科技有限公司 分离动物胚胎间质性干细胞并提取其分泌物的方法
WO2012137970A1 (ja) 2011-04-08 2012-10-11 国立大学法人大阪大学 改変ラミニンおよびその利用
WO2012145682A1 (en) * 2011-04-21 2012-10-26 Amgen Inc. A method for culturing mammalian cells to improve recombinant protein production
CN104884468B (zh) 2012-12-28 2018-08-31 国立大学法人大阪大学 附加有胶原结合性分子的改造层粘连蛋白及其利用
CN104651305A (zh) * 2015-02-13 2015-05-27 沈阳澔源生物科技有限公司 一种利用脐带间充质干细胞获取生物活性蛋白的方法
JP6849957B2 (ja) * 2015-11-10 2021-03-31 国立大学法人京都大学 ラミニンフラグメント含有培地を用いる細胞培養方法
RU2742828C2 (ru) * 2016-03-09 2021-02-11 Авита Интернэшнл Лтд. Применение стволовых клеток, экспрессирующих мезенхимальные и нейрональные маркеры, и их композиций для лечения неврологических заболеваний (варианты)
AU2018228352B2 (en) * 2017-02-28 2024-08-01 Centre Hospitalier Régional Universitaire De Nancy Mesenchymal stem cells obtained from Wharton's jelly for the treatment of sepsis
JP6469287B1 (ja) * 2018-06-22 2019-02-13 株式会社 バイオミメティクスシンパシーズ 中空糸細胞培養装置,細胞培養方法,培養上清の製造方法
JPWO2021200744A1 (https=) * 2020-03-31 2021-10-07

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3009502A1 (en) * 2013-06-12 2016-04-20 Osaka University Cell culture equipment coated with laminin fragments in dry state
EP3170892A1 (en) * 2014-07-16 2017-05-24 Osaka University Method for enhancing activity of laminin fragment cell culture substrate

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AU2021247879A1 (en) 2022-11-03
EP4155389A3 (en) 2023-07-12
JPWO2021200744A1 (https=) 2021-10-07
EP4130240A1 (en) 2023-02-08
CA3177567A1 (en) 2021-10-07
EP4130240A4 (en) 2024-05-08
EP4155389A2 (en) 2023-03-29
CN116179480A (zh) 2023-05-30
TW202311526A (zh) 2023-03-16
AU2022259729B2 (en) 2025-05-01
AU2022259729A1 (en) 2022-12-01
JP2024015245A (ja) 2024-02-01
US20230172992A1 (en) 2023-06-08
JP2022181218A (ja) 2022-12-07
WO2021200744A1 (ja) 2021-10-07
TW202204605A (zh) 2022-02-01
CN115362252A (zh) 2022-11-18
CA3173721A1 (en) 2021-10-07

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