CN103502440A - 毛发颜色受控制的移植用再生毛囊原基的制造方法、包含移植用再生毛囊原基的组合物和再生毛囊原基的移植方法 - Google Patents
毛发颜色受控制的移植用再生毛囊原基的制造方法、包含移植用再生毛囊原基的组合物和再生毛囊原基的移植方法 Download PDFInfo
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- 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
- C12N5/0628—Hair stem cells; Hair progenitors
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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
- C12N5/0629—Keratinocytes; Whole skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/18—Materials or treatment for tissue regeneration for hair reconstruction
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- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/09—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from epidermal cells, from skin cells, from oral mucosa cells
- C12N2506/092—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from epidermal cells, from skin cells, from oral mucosa cells from hair cells
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- 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
- C12N2506/1346—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells
- C12N2506/1376—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells from mesenchymal stem cells derived from hair follicles
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Abstract
Description
Claims (15)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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JP2011-038777 | 2011-02-24 | ||
JP2011038777 | 2011-02-24 | ||
PCT/JP2012/054055 WO2012115079A1 (ja) | 2011-02-24 | 2012-02-21 | 毛色が制御された移植用再生毛包原基の製造方法、当該移植用再生毛包原基を含む組成物、およびその移植方法 |
Publications (2)
Publication Number | Publication Date |
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CN103502440A true CN103502440A (zh) | 2014-01-08 |
CN103502440B CN103502440B (zh) | 2016-06-29 |
Family
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Application Number | Title | Priority Date | Filing Date |
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CN201280010080.8A Expired - Fee Related CN103502440B (zh) | 2011-02-24 | 2012-02-21 | 毛发颜色受控制的移植用再生毛囊原基的制造方法、包含移植用再生毛囊原基的组合物和再生毛囊原基的移植方法 |
Country Status (12)
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US (1) | US9321998B2 (zh) |
EP (1) | EP2679674B1 (zh) |
JP (1) | JP5887333B2 (zh) |
KR (1) | KR101854490B1 (zh) |
CN (1) | CN103502440B (zh) |
AU (1) | AU2012221254B2 (zh) |
CA (1) | CA2827853C (zh) |
ES (1) | ES2727041T3 (zh) |
RU (1) | RU2013142280A (zh) |
SG (2) | SG192924A1 (zh) |
TW (1) | TWI546384B (zh) |
WO (1) | WO2012115079A1 (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108324993A (zh) * | 2018-01-15 | 2018-07-27 | 上海神因生物科技有限公司 | 一种诱导毛发再生的干细胞复合体、其制备方法及应用 |
CN111148826A (zh) * | 2017-09-29 | 2020-05-12 | 凸版印刷株式会社 | 细胞移植装置以及细胞移植用单元 |
CN113710795A (zh) * | 2018-09-26 | 2021-11-26 | 株式会社器官再生工学 | 毛囊上皮干细胞的体外增殖方法 |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10478526B2 (en) | 2013-05-03 | 2019-11-19 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Skin substitutes and methods for hair follicle neogenesis |
EP3351621B1 (en) * | 2015-10-30 | 2023-11-22 | National University Corporation Yokohama National University | Regenerated hair follicle primordium aggregation manufacturing method, hair follicle tissue-containing sheet, and method for manufacturing hair follicle tissue-containing sheet |
US20190201579A1 (en) | 2016-06-21 | 2019-07-04 | Organ Technologies, Inc. | Method for manufacturing artificial skin having hair follicles, sebaceous glands, and hair pores |
CN110167609A (zh) * | 2016-11-10 | 2019-08-23 | 奥加诺沃公司 | 生物打印的毛囊及其用途 |
FR3061207B1 (fr) * | 2016-12-23 | 2023-03-10 | Oreal | Utilisation des cellules germinales pour la preparation d’un microfollicule pileux |
US20200208106A1 (en) * | 2017-08-22 | 2020-07-02 | National University Corporation Yokohama National University | Production Method of Multiple Regenerated Hair Follicle Primordia, Production Method of Hair Follicle Tissue-Containing Sheet, Hair Regeneration Kit and Method for Screening Hair Growth promoter or Hair Growth Inhibitor |
FR3072972B1 (fr) * | 2017-10-30 | 2023-03-10 | Oreal | Procede de preparation in vitro d’equivalents de papille dermique et de follicule pileux |
JP7158676B2 (ja) * | 2018-05-16 | 2022-10-24 | 国立大学法人横浜国立大学 | 再生毛の色制御方法、毛の再生方法及び毛包原基の製造方法 |
EP3805368A4 (en) * | 2018-06-04 | 2022-03-30 | Organ Technologies, Inc. | METHOD FOR THE PRODUCTION OF REGENERATIVE HAIR FOLLICLE GERMS |
JP7303962B2 (ja) * | 2019-03-14 | 2023-07-06 | 国立大学法人横浜国立大学 | 培養容器、及び細胞-担体複合体の製造方法 |
JP2022059393A (ja) * | 2020-10-01 | 2022-04-13 | 国立大学法人横浜国立大学 | 組織体の製造方法及び組織体を用いた疾患の治療方法 |
CN113082055B (zh) * | 2021-04-14 | 2022-09-06 | 济南磐升生物技术有限公司 | 一种再生有色毛发注射剂及其制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1551726A (zh) * | 2001-09-06 | 2004-12-01 | ������������ʽ���� | 毛囊重建系统及其载体动物 |
JP2009035514A (ja) * | 2007-08-02 | 2009-02-19 | Kanazawa Univ | Xvii型コラーゲンに関する異常分化抑制剤 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040068284A1 (en) * | 2002-01-29 | 2004-04-08 | Barrows Thomas H. | Method for stimulating hair growth and kit for carrying out said method |
DE10327879A1 (de) | 2003-06-18 | 2005-01-05 | Henkel Kgaa | Rekonstruierte dermale Papille |
CA2610474C (en) | 2005-05-30 | 2015-02-24 | Tokyo University Of Science Educational Foundation Administrative Organization | Method of producing tooth, set of teeth, and method of producing tissue |
GB0605450D0 (en) | 2006-03-17 | 2006-04-26 | Intercytex Ltd | Cell co-culture |
JP4991204B2 (ja) | 2006-07-31 | 2012-08-01 | 株式会社オーガンテクノロジーズ | 歯の製造方法 |
JP4991203B2 (ja) | 2006-07-31 | 2012-08-01 | 株式会社オーガンテクノロジーズ | 歯の製造方法 |
JP5069572B2 (ja) | 2007-01-22 | 2012-11-07 | 株式会社オーガンテクノロジーズ | 間葉系細胞の製造方法、歯の製造方法及び歯形成用間葉系細胞 |
JP2008206500A (ja) | 2007-02-28 | 2008-09-11 | Tokyo Univ Of Science | 歯の製造方法及びこれにより得られた歯 |
US7985537B2 (en) | 2007-06-12 | 2011-07-26 | Aderans Research Institute, Inc. | Methods for determining the hair follicle inductive properties of a composition |
EP2105499A1 (en) * | 2008-03-28 | 2009-09-30 | Technische Universität Berlin | Methods for producing de novo papillae and hair microfollicles and their use for in vitro tests and in vivo implantations |
-
2012
- 2012-02-21 WO PCT/JP2012/054055 patent/WO2012115079A1/ja active Application Filing
- 2012-02-21 SG SG2013063979A patent/SG192924A1/en unknown
- 2012-02-21 JP JP2013501043A patent/JP5887333B2/ja not_active Expired - Fee Related
- 2012-02-21 KR KR1020137024254A patent/KR101854490B1/ko active IP Right Grant
- 2012-02-21 RU RU2013142280/10A patent/RU2013142280A/ru not_active Application Discontinuation
- 2012-02-21 EP EP12749896.2A patent/EP2679674B1/en active Active
- 2012-02-21 US US14/000,939 patent/US9321998B2/en not_active Expired - Fee Related
- 2012-02-21 CN CN201280010080.8A patent/CN103502440B/zh not_active Expired - Fee Related
- 2012-02-21 SG SG10201600631SA patent/SG10201600631SA/en unknown
- 2012-02-21 ES ES12749896T patent/ES2727041T3/es active Active
- 2012-02-21 CA CA2827853A patent/CA2827853C/en not_active Expired - Fee Related
- 2012-02-21 AU AU2012221254A patent/AU2012221254B2/en not_active Ceased
- 2012-02-24 TW TW101106174A patent/TWI546384B/zh not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1551726A (zh) * | 2001-09-06 | 2004-12-01 | ������������ʽ���� | 毛囊重建系统及其载体动物 |
JP2009035514A (ja) * | 2007-08-02 | 2009-02-19 | Kanazawa Univ | Xvii型コラーゲンに関する異常分化抑制剤 |
Non-Patent Citations (1)
Title |
---|
ASAKAWA,KYOSUKE,ET AL: "Moho Saisei ni Yoru Mohatsu no Kinoteki Saisei II Seitai Mouse Hohige Moho Yurai Saibo o Mochiita Saisei Moho Genki Ishoku ni Yoru Ke no Saisei", 《REGENERATIVE MEDICINE》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111148826A (zh) * | 2017-09-29 | 2020-05-12 | 凸版印刷株式会社 | 细胞移植装置以及细胞移植用单元 |
CN108324993A (zh) * | 2018-01-15 | 2018-07-27 | 上海神因生物科技有限公司 | 一种诱导毛发再生的干细胞复合体、其制备方法及应用 |
CN108324993B (zh) * | 2018-01-15 | 2020-11-03 | 朱剑虹 | 一种诱导毛发再生的干细胞复合体、其制备方法及应用 |
CN113710795A (zh) * | 2018-09-26 | 2021-11-26 | 株式会社器官再生工学 | 毛囊上皮干细胞的体外增殖方法 |
Also Published As
Publication number | Publication date |
---|---|
US20140052167A1 (en) | 2014-02-20 |
KR20140006033A (ko) | 2014-01-15 |
WO2012115079A1 (ja) | 2012-08-30 |
SG192924A1 (en) | 2013-09-30 |
AU2012221254B2 (en) | 2016-05-12 |
JPWO2012115079A1 (ja) | 2014-07-07 |
SG10201600631SA (en) | 2016-02-26 |
TWI546384B (zh) | 2016-08-21 |
EP2679674A4 (en) | 2014-12-03 |
TW201309800A (zh) | 2013-03-01 |
CA2827853C (en) | 2019-04-16 |
AU2012221254A1 (en) | 2013-09-12 |
KR101854490B1 (ko) | 2018-05-03 |
EP2679674A1 (en) | 2014-01-01 |
EP2679674B1 (en) | 2019-04-24 |
RU2013142280A (ru) | 2015-03-27 |
CA2827853A1 (en) | 2012-08-30 |
JP5887333B2 (ja) | 2016-03-16 |
CN103502440B (zh) | 2016-06-29 |
ES2727041T3 (es) | 2019-10-11 |
US9321998B2 (en) | 2016-04-26 |
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