Stem Cell Derived Human Neurons in CNS Drug Discovery
Poster Feb 21, 2008
L Jackson, C Verastegui, C Wells, D Pau, A Nunn, A Finucane, M Lynch, S Boldt, L Gerrard, S.J. MacKenzie
Central nervous system disorders affect many people worldwide. To increase the quality and number of drugs available for treatments of CNS disorders such as Alzheimer’s, schizophrenia and anxiety, the success rate of CNS drug discovery programmes must be improved. The challenge in drug discovery is to develop more relevant assay systems to identify lead compounds for further development. Cell based screening assays currently used for CNS drug development involve primary cells or commercially available cell lines, both of which have many disadvantages. Here, we have overcome these limitations by generating unlimited supplies of physiologically relevant neurons from human stem cells. These neurons can be successfully maniplulated and used in CNS drug discovery programmes to identify lead candidate compounds and limit the need for in vivo experimentation.
We found a distinct subpopulation of Tregs within BMSCs. Tregs and BMSCs in co-culture conferred neuroprotection that varied in a dose-dependent manner. Tregs minimized stem cell production of IL-6, a pro-inflammatory cytokine, and inhibited BMSC secretion of FGF-beta, a cytokine related to BMSC proliferation and differentiation. The ratio of Tregs found natively in BMSCs is optimally adapted to provide the maximum neuroprotective benefit of stem cell treatment after ischemic stroke.READ MORE
We utilized paired synthetic crRNAs coupled with our synthetic tracrRNA in cells transduced with lentiviral Cas9 to perform a functional knockout on hsa-miR-221. This three-part system (crRNA, tracrRNA and Cas9) has demonstrated efficient gene editing when used with only one guide RNA, but the goal was to use two crRNAs to remove the entire stem-loop.READ MORE