Examenspresentation Christoffer Hagström
Titel: Screening of a drug library for inducers or inhibitors of the osteoarthritis associated gene Aggrecan
- Datum:Startar 5 april 2023, 10:00Slutar 5 april 2023, 11:00
- Språk:Svenska och engelska
Supervisor: Stina Simonsson, Sahlgrenska Sjukhuset
Examiner: Sabine Reinfeldt, E2
Osteoarthritis (OA) is a degenerative cartilage disease which causes pain and im¬pacts the quality of life for millions of people worldwide.
Here an induced pluripotent stems cell line (iPSC)-line, genetically modified with the green fluorescence protein (GFP) inserted under the OA associated gene aggrecan (ACAN), has been used. Cell pellets of two hundred thousands of cells per pellet were formed and differentiated into cartilage tissue. Using these pellets we performed high-throughput screen of drugs most approved by the FDA (US Food and Drug Administration) to identify inducers or inhibitors of the ACAN gene monitored over an 8 week time period using high throughput confocal microscopy equipped with Artificial Intelligence (AI) image analysis program to identify GFP signals in the three dimensional pellets.
The result show that 19 out of the 1120 different drugs tested herein had a significant effect on ACAN in the pellets. Fifteen drugs were identified as inducers and four as inhibitors. One of our identified inducers has recently shown to have a positive impact on cartilage regeneration in mice. Together, these data suggests that this method can serve to identify cartilage improving drugs and possible candidates for OA therapeutics. Therefore, these are suggested for further evaluation in animal studies or clinical trials since the identified drugs are FDA approved.