22-11-2018 дата публикации
Номер: US20180334646A1
The present invention is based in part on the discovery of significant improvements to cell culture systems and methods of generating organoids. The system of the invention provides a novel spinning bioreactor platform for higher-throughput 3D culturing of stem cells (e.g. human induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs)). The system can be widely used as a standard platform to generate stem cell-derived human organoids for any tissue and for high-throughput drug screenings, toxicity testing, and modeling normal human organ development and diseases. 1. A cell culture system , comprising i) a base substrate having a plurality of culture wells; and', 'ii) a shaft operably associated with each culture well, each shaft being configured to mix media present in each culture well and having a gear adapted to operably associate with a gear on a shaft associated with an adjacent culture well; and, 'a) a multiwell culture plate, the plate comprisingb) a motor having a drive shaft in operable communication with the shaft gears, wherein rotation of the drive shaft causes rotation of each shaft and mixing of the media in each culture well.2. The cell culture system of claim 1 , wherein each shaft is disposed in a cover plate overlying the base substrate.3. The cell culture system of claim 1 , wherein the drive shaft is in operable connection with the shaft gears via an intermediate drive gear connected to the drive shaft.4. The cell culture system of claim 1 , wherein each shaft comprises one or more fins disposed on the shaft for mixing media.5. The cell culture system of claim 4 , wherein each fin is tilted along the longitudinal axis of the shaft.6. The cell culture system of claim 1 , wherein the multiwell culture plate comprises between 6 to 48 culture wells.7. The cell culture system of claim 1 , further comprises a second multiwell culture plate claim 1 , the second multiwell culture plate comprising:a) a base substrate having a plurality of ...
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