RU2018132199A - Дифференцировка эмбриональных стволовых клеток человека в одногормональные инсулинположительные клетки - Google Patents
Дифференцировка эмбриональных стволовых клеток человека в одногормональные инсулинположительные клетки Download PDFInfo
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- C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
Claims (18)
1. Способ получения одногормональных клеток, включающий:
(a) дифференцировку клеток поджелудочной железы передней кишки в клетки энтодермы поджелудочной железы путем обработки клеток поджелудочной железы передней кишки ингибитором shh, низкой дозой ретиноевой кислоты и аскорбиновой кислотой; и
(b) дифференцировку клеток энтодермы поджелудочной железы в одногормональные эндокринные клетки поджелудочной железы в среде, дополненной ингибитором shh, низкой дозой ретиноевой кислоты и аскорбиновой кислотой.
2. Способ по п.1, в котором клетки энтодермы поджелудочной железы экспрессируют PDX-1, более высокий уровень NKX6.1 и более низкий уровень SOX2 по сравнению с клетками поджелудочной железы передней кишки.
3. Способ по п.1, в котором стадия (а) дополнительно включает обработку активатором PKC и ингибитором рецептора BMP.
4. Способ по п.3, в котором активатор PKC представляет собой TPB.
5. Способ по п. 3 или 4, в котором ингибитор BMP представляет собой LDN-193189.
6. Способ по п.3, в котором стадия (а) включает обработку с использованием 0,25 мкМ SANT-1, 200 нМ TPB, 50 нМ ретиноевой кислоты, 200 нМ TPB, 50 нМ LDN-193189 и 0,1 мМ аскорбиновой кислоты.
7. Способ по п.1, в котором стадия (b) дополнительно включает обработку ингибитором ALK5.
8. Способ по п.7, в котором ингибитор ALK5 представляет собой ингибитор ALK5 II.
9. Способ по п.7, в котором ингибитор ALK5 представляет собой SD208.
10. Способ по п.7, в котором стадия (b) включает обработку с использованием 0,1 мМ аскорбиновой кислоты, 50 нМ ретиноевой кислоты, 0,25 мкМ SANT-1 и 1 мкМ ингибитора Alk5.
11. Способ по любому из пп. 1, 3 или 7, где ингибитор shh на стадии (a), (b) или (a) и (b) представляет собой SANT-1.
12. Способ по любому из пп. 1, 3 или 7, где способ на стадии (a), (b) или (a) и (b) включает обработку с использованием от 0,01 мМ до 1 мМ аскорбиновой кислоты.
13. Способ по любому из пп.1, 3 или 7, где способ на стадии (a), (b) или (a) и (b) включает обработку с использованием от 0,1 мМ до 0,5 мМ аскорбиновой кислоты.
14. Способ по любому из пп.1, 3 или 7, где способ на стадии (a), (b) или (a) и (b) включает обработку в среде, содержащей менее 25 мМ глюкозы.
15. Способ по п.14, в котором концентрация глюкозы находится в диапазоне от 8 мМ до 20 мМ глюкозы.
16. Способ по п.1, в котором клетки поджелудочной железы передней кишки представляют собой клетки поджелудочной железы передней кишки человека.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US201161579351P | 2011-12-22 | 2011-12-22 | |
US61/579,351 | 2011-12-22 |
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RU2014130042A Division RU2668798C2 (ru) | 2011-12-22 | 2012-12-07 | Способы in vitro пошаговой дифференцировки полюрипотентных клеток |
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RU2018132199A true RU2018132199A (ru) | 2018-10-31 |
RU2018132199A3 RU2018132199A3 (ru) | 2019-05-24 |
RU2705001C2 RU2705001C2 (ru) | 2019-11-01 |
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RU2018132199A RU2705001C2 (ru) | 2011-12-22 | 2012-12-07 | Дифференцировка эмбриональных стволовых клеток человека в одногормональные инсулинположительные клетки |
RU2014130042A RU2668798C2 (ru) | 2011-12-22 | 2012-12-07 | Способы in vitro пошаговой дифференцировки полюрипотентных клеток |
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RU2014130042A RU2668798C2 (ru) | 2011-12-22 | 2012-12-07 | Способы in vitro пошаговой дифференцировки полюрипотентных клеток |
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US (4) | US9388386B2 (ru) |
EP (1) | EP2794857A4 (ru) |
JP (4) | JP6441080B2 (ru) |
KR (2) | KR102203056B1 (ru) |
CN (1) | CN105143446B (ru) |
AR (1) | AR089426A1 (ru) |
AU (3) | AU2012355698B2 (ru) |
BR (1) | BR112014015417A8 (ru) |
CA (1) | CA2860107C (ru) |
HK (1) | HK1203552A1 (ru) |
MX (1) | MX2014007744A (ru) |
PH (1) | PH12014501429A1 (ru) |
RU (2) | RU2705001C2 (ru) |
SG (2) | SG11201403473QA (ru) |
WO (1) | WO2013095953A1 (ru) |
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