DK3042951T3 - Hidtil ukendt fremgangsmåde til at inducere dopamin-producerende neurale precursorceller - Google Patents
Hidtil ukendt fremgangsmåde til at inducere dopamin-producerende neurale precursorceller Download PDFInfo
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Claims (9)
1. Fremgangsmåde til at fremstille dopaminerge neuronprogenitorceller fra pluripotente stamceller, hvor fremgangsmåden omfatter trinnene: (i) at udføre adhærent dyrkning af pluripotente stamceller på en ekstracellulær matrix i et medie indeholdende et reagens(er) valgt fra gruppen bestående af BMP-inhibitor, TGFp-inhibitor, SHH signalstimulerende middel, FGF8 og GSK3p-inhibitor; (ii) at opsamle Corin- og/eller Lrtml-positive celler fra cellerne opnået i trin (i) under anvendelse af et stof, der binder til Corin, og/eller et stof der binder til Lrtml, hvor stoffet, der binder til Corin, eller stoffet, der binder til Lrtml, er et antistof eller en aptamer, der binder til Corin eller Lrtml; og (iii) at udføre suspensiondyrkning af cellerne opnået i trin (ii) i et medie indeholdende en neurotrofisk faktor, hvor trinnet (iii) udføres i 14 til 21 dage.
2. Fremgangsmåde ifølge krav 1, hvor trin (i) omfatter trinnene: (a) at udføre adhærent dyrkning af pluripotente stamceller på en ekstracellulær matrix i et medie indeholdende BMP-inhibitor og TGFp-inhibitor; (b) at udføre adhærent dyrkning af cellerne opnået i trin (a) på en ekstracellulær matrix i et medie indeholdende BMP-inhibitor, TGFp-inhibitor, SHH signal-stimulerende middel og FGF8; (c) at udføre adhærent dyrkning af cellerne opnået i trin (b) på en ekstracellulær matrix i et medie indeholdende BMP-inhibitor, TGFp-inhibitor, SHH signal-stimulerende middel, FGF8 og GSK3p-inhibitor; og (d) at udføre adhærent dyrkning af cellerne opnået i trin (c) på en ekstracellulær matrix i et medie indeholdende BMP-inhibitor og GSK3p-inhibitor.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor den neurotrofiske faktor er BDNF og GDNF.
4. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 3, hvor mediet i trin (iii) endvidere omfatter B27 supplement, ascorbinsyre og dibutyryl cyklisk AMP.
5. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 4, hvor trinnet (i) udføres i mindst 10 dage.
6. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 5, hvor trinnet (i) udføres i 12 dage til 21 dage.
7. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 6, hvor den ekstracellulære matrix er laminin eller et fragment(er) deraf.
8. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 7, hvor den ekstracellulære matrix er laminin 511E8.
9. Terapeutisk middel til anvendelse til behandling af Parkinsons sygdom, omfattende dopaminerge neuronprogenitorceller opnået med fremgangsmåden ifølge et hvilket som helst af kravene 1 til 8.
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| CN110872576A (zh) * | 2019-06-06 | 2020-03-10 | 中国科学院广州生物医药与健康研究院 | 一种将小鼠成纤维细胞转分化为多巴胺能神经元的方法 |
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| AU2014316100A1 (en) | 2016-04-14 |
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| KR102320537B1 (ko) | 2021-11-01 |
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