RU2013110127A - Конверсия соматических клеток в индуцированные репрограмированные нейрональные стволовые клетки (ирнск) - Google Patents
Конверсия соматических клеток в индуцированные репрограмированные нейрональные стволовые клетки (ирнск) Download PDFInfo
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Abstract
1. Способ получения нейральных стволовых клеток (НСК), включающий:а) получение соматических клеток,б) репрограммирование указанных соматических клеток в НСК с помощью введения по меньшей мере двух генов из группы Bmi1, Sox2, Mash1, Sox11, Emx2, Foxg1 и Рах6; ив) индукцию репрограммирования с помощью ростовых факторов и малой молекулы.2. Способ по п.1, дополнительно включающийг) инкубацию продуктов стадий б) и в) в условиях, подходящих для пролиферации НСК.3. Способ по п.1, где соматические клетки стадии а) являются клетками человека.4. Способ по п.1, где соматические клетки стадии а) выбраны из группы фибробластов, кератиноцитов или адипоцитов.5. Способ по п.1, где факторы роста и малая молекула стадии в) являются добавками в среду определенного химического состава.6. Способ по п.5, где среда определенного химического состава является бессывороточной средой с добавлением инсулина, трансферрина и прогестерона.7. Способ по п.1, где по меньшей мере два гена стадии б) включают Bmi1 и Sox2.8. Способ по п.7, где по меньшей мере два гена стадии б) дополнительно включают по меньшей мере один ген, выбранный из группы Mash1, Sox11, Emx2, Foxg1 и Рах6.9. Способ по п.7 или п.8, где по меньшей мере два гена стадии б) включают Bmi, Sox2 и Mash1.10. Способ по п.1, где фактор роста стадии в) выбран из группы FGF2, EGF и BDNF.11. Способ по п.1, где малая молекула стадии в) включает ингибитор ROCK.12. Способ по п.11, где ингибитор ROCK выбран из группы 1-(5-изокинолинсульфонил)гомопиперазина, N-бензил-2-(пиримидин-4-иламино)тиазол-4-карбоксамида, (+)-(R)-транс-4-(1-аминоэтил)-N-(4-пиридил)циклогексанкарбоксамида дигидрохлорида и N-{(3R,4R)-4-[4-(2-фтор-6-гидрокси-3-метокси-бензоил)-бензоиламино]-азепан-3-ил}-4-гидрокси-3,5-диметилбензамида.
Claims (19)
1. Способ получения нейральных стволовых клеток (НСК), включающий:
а) получение соматических клеток,
б) репрограммирование указанных соматических клеток в НСК с помощью введения по меньшей мере двух генов из группы Bmi1, Sox2, Mash1, Sox11, Emx2, Foxg1 и Рах6; и
в) индукцию репрограммирования с помощью ростовых факторов и малой молекулы.
2. Способ по п.1, дополнительно включающий
г) инкубацию продуктов стадий б) и в) в условиях, подходящих для пролиферации НСК.
3. Способ по п.1, где соматические клетки стадии а) являются клетками человека.
4. Способ по п.1, где соматические клетки стадии а) выбраны из группы фибробластов, кератиноцитов или адипоцитов.
5. Способ по п.1, где факторы роста и малая молекула стадии в) являются добавками в среду определенного химического состава.
6. Способ по п.5, где среда определенного химического состава является бессывороточной средой с добавлением инсулина, трансферрина и прогестерона.
7. Способ по п.1, где по меньшей мере два гена стадии б) включают Bmi1 и Sox2.
8. Способ по п.7, где по меньшей мере два гена стадии б) дополнительно включают по меньшей мере один ген, выбранный из группы Mash1, Sox11, Emx2, Foxg1 и Рах6.
9. Способ по п.7 или п.8, где по меньшей мере два гена стадии б) включают Bmi, Sox2 и Mash1.
10. Способ по п.1, где фактор роста стадии в) выбран из группы FGF2, EGF и BDNF.
11. Способ по п.1, где малая молекула стадии в) включает ингибитор ROCK.
12. Способ по п.11, где ингибитор ROCK выбран из группы 1-(5-изокинолинсульфонил)гомопиперазина, N-бензил-2-(пиримидин-4-иламино)тиазол-4-карбоксамида, (+)-(R)-транс-4-(1-аминоэтил)-N-(4-пиридил)циклогексанкарбоксамида дигидрохлорида и N-{(3R,4R)-4-[4-(2-фтор-6-гидрокси-3-метокси-бензоил)-бензоиламино]-азепан-3-ил}-4-гидрокси-3,5-диметилбензамида.
13. Способ по п.1, где соматические клетки предварительно обработаны ингибитором деацетилазы гистонов (HDAC).
14. Способ по п.1, где репрограммирование указанных соматических клеток достигается доставкой комбинации по меньшей мере двух генов с помощью лентивируса.
15. Нейральные стволовые клетки, полученные способом по любому из пп.1-14.
16. Применение нейральных стволовых клеток по п.15 в качестве in vitro модели заболеваний ЦНС.
17. Терапевтическая композиция, включающая нейральные стволовые клетки по п.15.
18. Терапевтическая композиция по п.17, где нейральные стволовые клетки дифференцируются в нейроны или клетки глии.
19. Биобанк НСК, полученных с помощью способа по любому из пп.1-14.
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BR112013003031A2 (pt) | 2010-08-19 | 2016-06-14 | Hoffmann La Roche | método de produção de células hastes neurais (chn), células hastes neurais e seu uso, composição terapêutica e banco biológico de nscs |
CN102604894B (zh) | 2012-02-29 | 2014-07-30 | 中国科学院广州生物医药与健康研究院 | 用于制备神经干细胞的培养基及其用途 |
PL223189B1 (pl) * | 2012-11-15 | 2016-10-31 | Celther Polska Spółka Z Ograniczoną Odpowiedzialnością | Komórka iNS oraz sposób reprogramowania komórek somatycznych za pomocą czynnika Sox2 oraz Sox2 i c-Myc do komórki iNS |
EA035349B1 (ru) * | 2012-11-21 | 2020-05-29 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | ЗАМЕЩЕННЫЕ ПИРИМИДИНОВЫЕ ОБРАТНЫЕ ИНГИБИТОРЫ Bmi-1 |
KR20140121317A (ko) | 2013-04-06 | 2014-10-15 | 서울대학교산학협력단 | 비신경 세포로부터 유도 신경 줄기 세포의 생산 방법 및 이에 의하여 생산되는 유도 신경 줄기 세포 |
EP3024928B1 (en) | 2013-07-23 | 2018-11-21 | F. Hoffmann-La Roche AG | Small molecule based conversion of somatic cells into neural crest cells |
CN104342401B (zh) * | 2013-07-25 | 2017-04-05 | 中国科学院广州生物医药与健康研究院 | 利用确定的细胞因子组合促进成纤维细胞转分化为脂肪细胞 |
DK3060237T3 (da) * | 2013-10-25 | 2021-10-25 | Univ Wayne State | Modificeret omprogrammeringsprotein til anvendelse i behandling af cancer |
EP3088415B1 (en) | 2013-12-25 | 2019-11-06 | Toagosei Co., Ltd. | Method for inducing differentiation of pluripotent stem cells into endodermal cells |
CN104894060B (zh) * | 2014-03-03 | 2018-11-06 | 中国科学院上海生命科学研究院 | 诱导体细胞转分化为神经干细胞的方法及其应用 |
CN104195108B (zh) * | 2014-07-29 | 2018-02-06 | 深圳市三启生物技术有限公司 | 蛋白激酶抑制剂在从非神经细胞制备神经细胞中的用途 |
EP3265556A4 (en) * | 2015-03-04 | 2018-08-22 | The University of North Carolina at Chapel Hill | Methods for making neural stem cells and uses thereof |
US11027047B2 (en) | 2015-03-31 | 2021-06-08 | The University Of North Carolina At Chapel Hill | Delivery vehicles for stem cells and uses thereof |
JP6691756B2 (ja) | 2015-09-29 | 2020-05-13 | 東亞合成株式会社 | 合成ペプチドを用いた神経幹細胞の生産方法 |
ES2852998T4 (es) * | 2015-11-12 | 2024-04-25 | Hoffmann La Roche | Oligonucleótidos para inducir la expresión de UBE3A paterno |
CA3019089A1 (en) * | 2016-03-31 | 2017-10-05 | Ajinomoto Co., Inc. | Medium for neural stem cells enhancing neural differentiation ability |
EP3447126A4 (en) * | 2016-04-20 | 2019-11-13 | Kyoto Prefectural Public University Corporation | PROCESS FOR PRODUCING SHEET OF CULTIVATED EPITHELIAL CELLS |
WO2019004533A1 (ko) * | 2017-06-30 | 2019-01-03 | 주식회사 스템랩 | 소변세포로부터 케라티노사이트 줄기세포로의 직접 역분화 방법 및 역분화된 케라티노사이트 줄기세포를 이용한 피부재생 촉진용 조성물의 제조방법 |
EP3807402A4 (en) * | 2018-06-14 | 2022-04-27 | Academia Sinica | METHOD FOR GENERATE INDUCED OLIGODENDROCYTE LINEAGE CELLS AND TREATMENT USING SUCH CELLS |
WO2020038851A1 (en) | 2018-08-21 | 2020-02-27 | F. Hoffmann-La Roche Ag | Methods for assessing transendothelial barrier integrity |
AU2020453143A1 (en) * | 2020-06-09 | 2023-02-09 | Unist(Ulsan National Institute Of Science And Technology) | Composition for inducing direct cross differentiation of somatic cell into motor neuron, and method for using same |
CA3197178A1 (en) * | 2020-09-29 | 2022-04-07 | NeuExcell Therapeutics Inc. | Neurod1 combination vector |
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WO2004007700A1 (ja) * | 2002-06-24 | 2004-01-22 | Tanabe Seiyaku Co., Ltd. | 神経系細胞の製造方法 |
US7682828B2 (en) | 2003-11-26 | 2010-03-23 | Whitehead Institute For Biomedical Research | Methods for reprogramming somatic cells |
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US8278104B2 (en) * | 2005-12-13 | 2012-10-02 | Kyoto University | Induced pluripotent stem cells produced with Oct3/4, Klf4 and Sox2 |
US20100021437A1 (en) * | 2008-04-07 | 2010-01-28 | The McLean Hospital Corporation Whitehead Institute for Biomedical Research | Neural stem cells derived from induced pluripotent stem cells |
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ES2580837T3 (es) | 2016-08-29 |
WO2012022725A3 (en) | 2012-04-12 |
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MX2013001587A (es) | 2013-03-21 |
EP2606126A2 (en) | 2013-06-26 |
CA2807226A1 (en) | 2012-02-23 |
JP2013535973A (ja) | 2013-09-19 |
CN103068974A (zh) | 2013-04-24 |
BR112013003031A2 (pt) | 2016-06-14 |
US20140051171A1 (en) | 2014-02-20 |
US9297025B2 (en) | 2016-03-29 |
RU2562111C2 (ru) | 2015-09-10 |
WO2012022725A2 (en) | 2012-02-23 |
HK1184492A1 (zh) | 2014-01-24 |
EP2606126B1 (en) | 2016-05-18 |
KR20160033798A (ko) | 2016-03-28 |
CN103068974B (zh) | 2016-05-11 |
US20160369234A1 (en) | 2016-12-22 |
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