Description
Microglia are tissue-resident macrophages of the brain parenchyma. They are essential for regulating brain development and homeostasis and play a key role in regulating inflammation. Microglia are also implicated in many neurological disorders, making them interesting targets for therapeutic intervention. Microglia have an embryonal ontogeny and self-renew throughout life without any peripheral input. Replacing dysfunctional microglia with healthy counterparts or genetically engineered counterparts is a promising approach to treat brain disorders. Our aim is to develop an in vivo microglia-replacement approach as a foundation for future microglial-based cell therapies. We have created genetic and pharmacological mouse models in which we can deplete the endogenous microglia allowing for engraftment of progenitor cells. Additionally, we optimized multiple protocols to differentiate induced pluripotent stem cells (iPSC) into microglia progenitors. Our results show that microglia progenitors can successfully engraft as microglia-like cells in the brain after intracranial injection, however they remain distinguishable from endogenous embryonal microglia highlighting the importance of ontogeny. We continue to optimize iPSC differentiation protocols to generate microglia progenitors that after engraftment are more capable of resembling their embryonal counterparts and we further optimize transplantation strategies to enable more translatable and efficient engraftment. This work will lay the basis for a new treatment strategy in which microglia can be engineered and microglia replacement can be used to effectively treat neurological disorders.| Period | 10 Oct 2024 |
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| Event title | Brayn conference Verona 2024: 7th Brainstorming research assembly for young neuroscientists |
| Event type | Conference |
| Location | Verona, Italy |
| Degree of Recognition | International |