RU2016133754A - Лечение диабета при помощи панкреатических эндокринных клеток-предшественников - Google Patents
Лечение диабета при помощи панкреатических эндокринных клеток-предшественников Download PDFInfo
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- 230000009996 pancreatic endocrine effect Effects 0.000 title claims 12
- 210000003890 endocrine cell Anatomy 0.000 title claims 2
- 206010012601 diabetes mellitus Diseases 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims 23
- 239000002243 precursor Substances 0.000 claims 11
- 210000001900 endoderm Anatomy 0.000 claims 8
- 238000000034 method Methods 0.000 claims 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 5
- 108091005735 TGF-beta receptors Proteins 0.000 claims 5
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 claims 5
- 239000008103 glucose Substances 0.000 claims 5
- 230000002401 inhibitory effect Effects 0.000 claims 5
- 229940043355 kinase inhibitor Drugs 0.000 claims 5
- 239000002609 medium Substances 0.000 claims 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 5
- 238000002054 transplantation Methods 0.000 claims 4
- 101100518002 Danio rerio nkx2.2a gene Proteins 0.000 claims 3
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 claims 3
- 102100027886 Homeobox protein Nkx-2.2 Human genes 0.000 claims 3
- 101100460496 Homo sapiens NKX2-2 gene Proteins 0.000 claims 3
- 239000008280 blood Substances 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- LBPKYPYHDKKRFS-UHFFFAOYSA-N 1,5-naphthyridine, 2-[3-(6-methyl-2-pyridinyl)-1h-pyrazol-4-yl]- Chemical group CC1=CC=CC(C2=C(C=NN2)C=2N=C3C=CC=NC3=CC=2)=N1 LBPKYPYHDKKRFS-UHFFFAOYSA-N 0.000 claims 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 claims 2
- 210000000683 abdominal cavity Anatomy 0.000 claims 2
- 239000002775 capsule Substances 0.000 claims 2
- 210000001671 embryonic stem cell Anatomy 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 210000000936 intestine Anatomy 0.000 claims 2
- 210000004185 liver Anatomy 0.000 claims 2
- 102000045246 noggin Human genes 0.000 claims 2
- 108700007229 noggin Proteins 0.000 claims 2
- 210000002747 omentum Anatomy 0.000 claims 2
- 210000000496 pancreas Anatomy 0.000 claims 2
- 210000001778 pluripotent stem cell Anatomy 0.000 claims 2
- 210000002784 stomach Anatomy 0.000 claims 2
- 238000007920 subcutaneous administration Methods 0.000 claims 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000005538 encapsulation Methods 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 210000003577 pancreatic endocrine progenitor Anatomy 0.000 claims 1
- 210000000130 stem cell Anatomy 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
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- C12N5/06—Animal cells or tissues; Human cells or tissues
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- C12N5/0676—Pancreatic cells
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Claims (24)
1. Применение популяции инкапсулированных панкреатических эндокринных клеток-предшественников в производстве лекарственного средства для снижения уровня глюкозы в крови у пациента, где панкреатические эндокринные клетки-предшественники дифференцируются in vitro из клеток, экспрессирующих маркеры, характерные для линии поджелудочной энтодермы, и где панкреатические эндокринные клетки-предшественники экспрессируют NKX2.2.
2. Применение по п.1, где применение включает трансплантацию популяции инкапсулированных панкреатических эндокринных клеток-предшественников в организм пациента.
3. Применение по п.2, где применение включает трансплантацию клеток в печень, естественную поджелудочную железу, пространство под почечной капсулой, сальник, брюшную полость, субсерозное пространство, кишечник, желудок или подкожный карман.
4. Применение по п.1, где клетки получены из плюрипотентных стволовых клеток.
5. Применение по п.4, где клетки получены из эмбриональных стволовых клеток человека.
6. Применение по п.1, где панкреатические эндокринные клетки-предшественники дифференцируются in vitro из клеток, экспрессирующих маркеры, характерные для линии поджелудочной энтодермы, в среде, дополненной фактором, способным ингибировать BMP, и ингибитором киназы TGF-β рецептора I.
7. Применение по п.6, где фактором, способным ингибировать BMP, является Ноггин.
8. Применение по п.6, где ингибитором киназы TGF-β рецептора I является ингибитор II ALK5.
9. Применение по п.6, где средой является DMEM, содержащая 4500 мг/л глюкозы и 1% B27.
10. Применение по п.6, где клетки культивируют в культуральной среде приблизительно 4 дня.
11. Применение по п.1, также включающее факторы роста, антиоксиданты или противовоспалительные вещества.
12. Применение по п.1, где пациент страдает диабетом I или II типа или подвергающегося риску его развития.
13. Способ снижения уровней глюкозы в крови у пациента с помощью инкапсулированных панкреатических клеток-предшественников, экспрессирующих NKX2.2, включающий:
культивирование клеток, экспрессирующих маркеры, характерные для линии поджелудочной энтодермы, в среде, дополненной фактором, способным ингибировать BMP, и ингибитором киназы TGF-β рецептора I, для дифференцировки клеток, экспрессирующих маркеры, характерные для линии поджелудочной энтодермы в панкреатические эндокринные клетки-предшественники;
инкапсулирование панкреатических эндокринных клеток-предшественников; и
трансплантацию инкапсулированных панкреатических эндокринных клеток-предшественников в организм пациента.
14. Способ снижения уровней глюкозы в крови у пациента с помощью инкапсулированных панкреатических эндокринных клеток-предшественников, экспрессирующих NKX2.2, включающий трансплантацию инкапсулированных панкреатических эндокринных клеток-предшественников в организм пациента,
где панкреатические эндокринные клетки-предшественники получены дифференцировкой клеток, экспрессирующих маркеры, характерные для линии панкреатической эндодермы, в среде, дополненной фактором, способным ингибировать BMP, и ингибитором киназы TGF-β рецептора I, для дифференцировки клеток, экспрессирующих маркеры, характерные для линии поджелудочной энтодермы в панкреатические эндокринные клетки-предшественники.
15. Способ по п.13 или 14, где трансплантация включает трансплантацию клеток в печень, естественную поджелудочную железу, пространство под почечной капсулой, сальник, брюшную полость, субсерозное пространство, кишечник, желудок или подкожный карман.
16. Способ по п.13 или 14, где фактором, способным ингибировать BMP, является Ноггин.
17. Способ по п.13 или 14, где ингибитором киназы TGF-β рецептора I является ингибитор II ALK5.
18. Способ по п.13 или 14, где средой является DMEM, содержащая 4500 мг/л глюкозы и 1% B27.
19. Способ по п.13 или 14, где клетки, экспрессирующие маркеры, характерные для линии поджелудочной энтодермы получены из плюрипотентных стволовых клеток.
20. Способ по п.13 или 14, где клетки, экспрессирующие маркеры, характерные для линии поджелудочной энтодермы получены из человеческих эмбриональных стволовых клеток.
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EP (2) | EP3981415A1 (ru) |
JP (5) | JP2013533319A (ru) |
KR (3) | KR20130100122A (ru) |
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US20220233298A1 (en) | 2019-05-31 | 2022-07-28 | W. L. Gore & Associates, Inc. | A biocompatible membrane composite |
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KR20190027969A (ko) | 2019-03-15 |
JP7012128B2 (ja) | 2022-01-27 |
EP2603226B1 (en) | 2021-04-07 |
JP2020196728A (ja) | 2020-12-10 |
EP2603226A4 (en) | 2014-01-15 |
RU2682719C2 (ru) | 2019-03-21 |
WO2012021698A3 (en) | 2012-05-10 |
CN103052393B (zh) | 2017-11-14 |
SG10201506264QA (en) | 2015-09-29 |
WO2012021698A2 (en) | 2012-02-16 |
JP2013533319A (ja) | 2013-08-22 |
US20120039955A1 (en) | 2012-02-16 |
CN103052393A (zh) | 2013-04-17 |
AU2011289379A1 (en) | 2013-02-07 |
EP3981415A1 (en) | 2022-04-13 |
DK2603226T3 (da) | 2021-06-07 |
KR20180032674A (ko) | 2018-03-30 |
JP2017031163A (ja) | 2017-02-09 |
JP2019131564A (ja) | 2019-08-08 |
MX2013001673A (es) | 2013-03-25 |
ZA201301836B (en) | 2018-12-19 |
CA2807158A1 (en) | 2012-02-16 |
JP2022058629A (ja) | 2022-04-12 |
SG187603A1 (en) | 2013-03-28 |
AR082674A1 (es) | 2012-12-26 |
BR112013003160A2 (pt) | 2016-06-28 |
RU2013110524A (ru) | 2014-09-20 |
EP2603226A2 (en) | 2013-06-19 |
RU2016133754A3 (ru) | 2018-12-10 |
KR20130100122A (ko) | 2013-09-09 |
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