The response of the central nervous system to injury and disease is a complex physiological process that involves the coordinated actions of many different cell types. The interplay of neural cells and vascular cells along with the innate and adaptive immune systems determines the response to different injury and disease stimuli and whether the central nervous system will repair or degenerate. Understanding this complex cellular environment is essential to understanding disease pathogenesis, elucidating underlying disease etiology, and developing treatments for neurological and psychiatric diseases. The goal of this conference will be to bring together people who study different aspects of neurological diseases and facilitate the interchange of ideas necessary for identifying new mechanisms underlying complex intercellular interactions in the diseased nervous system. This will include people who study resident neural cells (neurons, astrocytes, oligodendrocytes), vascular cells (blood-brain barrier, lymphatics, glymphatics) and immune cells (microglia, innate peripheral immune cells, adaptive immune cells) in the context of a variety of neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. Further, we will also attract people who implement different techniques including genetic mouse models, human iPSCs, invertebrate models, imaging, cell biology, and behavior in their research which will further facilitate exchange of ideas and foster collaboration. With the combined expertise at this conference, we will accelerate our ability to understand the complex neural response to injury and disease, which is a necessary step towards developing novel therapeutics for complex neurological diseases.
See the brochure for this Keystone Symposium.
Please see the poster presentation by FCDI’s Dr. Beatriz Freitas:
Title: Modeling Neuroinflammation using iPSC-derived engineered Microglia
Authors: Beatriz Freitas, Michael McLachlan, Sarah J Dickerson, Christie A Munn, Sarah A Burton, Abbey Musinsky, Madelyn Goedland, Michael Hancock, Deepika Rajesh, Simon Hilcove and Eugenia Jones
Abstract: Neuroinflammation and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Microglia, the resident immune cells of the brain, have emerged as key players in neuroinflammation. Human iPSC-derived microglia can serve as an authentic preclinical tool for understanding the pathobiology of neurodegenerative neurodevelopmental diseases. The present study involves the generation and characterization of genome engineered iPSC-derived iCell Microglia harboring heterozygous and homozygous mutations in the TREM2 gene, a single amino acid substitution in the SNCA (alpha-synuclein) gene to facilitate disease modelling for AD and PD, respectively. iCell Microglia were generated from both the engineered and non-engineered clones offering a unique isogenic pair for research applications.
Microglia were derived by differentiating cryopreserved and purified hematopoietic progenitor cells (HPCs) and further differentiating the HPCs to microglia using technology developed by the Blurton-Jones laboratory (Abud et al. Neuron 2017.) for which FujiFilm Cellular Dynamics Inc. has an exclusive license from the University of California-Irvine. End stage Microglia were characterized by morphology, quantification of TREM2, P2RY12, CX3CR1, IBA1, CD33 and CD45 levels by flow cytometry, quantification of phagocytic function using pHrodo BioParticles and aggregated amyloid beta, quantification of neuroinflammatory molecules by multiplex Luminex and quantification of soluble TREM levels and finally RNAseq analysis. Cryopreserved Microglia retained purity and function comparable to precryopreserved end stage Microglia. The results identified key differences in survival, kinetics of phagocytosis, and levels of molecules involved in neural inflammation between wild type (WT) and engineered microglia Thus, iPSC-derived isogenic WT and engineered microglia could serve as a powerful tool to gain insight into various physiological and pathological conditions associated with neurological disorders.