Equipment & Techniques
The aim of this research project is to provide new insights into the function and impact of exogenous (transplanted) senescent disease-associated induced Neural Stem Cells (iNSCs) within a 3D cellular environment using cerebral organoids. Fibroblasts from progressive Multiple Sclerosis (PMS) patients were reprogrammed into induced Neural Stem Cells (iNSCs), bypassing the pluripotency stage and retaining direct epigenetic hallmarks from the patient cells. Here they were discovered to have an inflammatory, premature senescent phenotype compared to age-matched counterparts. To understand how senescent NSCs may be altering their microenvironment within the PMS brain they were transplanted into cerebral organoids. Combining human based disease modelling, organoids, and state of the art interactome analysis, we aim to uncover new mechanisms by which progressive MS stem cells contribute to ongoing inflammation and neurodegeneration.