Concise Review: Modelling Neurodegenerative Diseases with Human Pluripotent Stem Cell Derived Microglia

Using iPSC microglia to model neuroinflammation AbstractInflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allow modelling of neurodegenerationin vitro. Several protocols for induced pluripotent stem cell (iPSC) ‐derived microglia have recently been developed and provide unlimited access to patient‐derived material. In this review, we give an overview of iPSC‐derived microglia models in mono‐culture and co‐culture systems, their advantages and limitations and how they have already been used for di sease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines as well as covering reporter cell lines which could help to elucidate complex cell interaction mechanisms in the microglia/neuron co‐culture system, for example, microglia induced synapse loss. Finally, we deliberate on how said co‐cultures could aid in personalized drug screening to identify patient‐specific therapies against neurodegenera...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research