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

Modelling of neurological diseases can be done in mono ‐cultures for many readouts, but for authentic modelling of neuron‐microglia interactions such as synapse pruning events it is crucial to use co‐cultures. AbstractInflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, 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 allows modeling of neurodegeneration in 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 present study, we give an overview of iPSC‐derived microglia models in mono‐culture and coculture systems, their advantages and limitations, and how they have already been used f or disease 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 coculture syste m, for example, microglia‐induced synapse...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research