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      Human iPSC-derived glia models for the study of neuroinflammation

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          Abstract

          Neuroinflammation is a complex biological process that plays a significant role in various brain disorders. Microglia and astrocytes are the key cell types involved in inflammatory responses in the central nervous system. Neuroinflammation results in increased levels of secreted inflammatory factors, such as cytokines, chemokines, and reactive oxygen species. To model neuroinflammation in vitro, various human induced pluripotent stem cell (iPSC)-based models have been utilized, including monocultures, transfer of conditioned media between cell types, co-culturing multiple cell types, neural organoids, and xenotransplantation of cells into the mouse brain. To induce neuroinflammatory responses in vitro, several stimuli have been established that can induce responses in either microglia, astrocytes, or both. Here, we describe and critically evaluate the different types of iPSC models that can be used to study neuroinflammation and highlight how neuroinflammation has been induced and measured in these cultures.

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          Most cited references147

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Neurotoxic reactive astrocytes are induced by activated microglia

            A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.
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              The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

              The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
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                Author and article information

                Contributors
                StoberlN@Cardiff.ac.uk
                MaguireE1@Cardiff.ac.uk
                SalisE@Cardiff.ac.uk
                ShawBJ@Cardiff.ac.uk
                Hall-RobertsH@Cardiff.ac.uk
                Journal
                J Neuroinflammation
                J Neuroinflammation
                Journal of Neuroinflammation
                BioMed Central (London )
                1742-2094
                10 October 2023
                10 October 2023
                2023
                : 20
                : 231
                Affiliations
                GRID grid.5600.3, ISNI 0000 0001 0807 5670, UK Dementia Research Institute (UK DRI), School of Medicine, , Cardiff University, ; Cardiff, CF10 3AT UK
                Article
                2919
                10.1186/s12974-023-02919-2
                10566197
                37817184
                261aa17a-a957-4980-a69b-adc72f651aad
                © BioMed Central Ltd., part of Springer Nature 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 7 June 2023
                : 2 October 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100017510, UK Dementia Research Institute;
                Award ID: UK DRI-DSI2020-IPMAR
                Funded by: GW4 BioMed MRC Doctoral Training Partnership
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Neurosciences
                induced pluripotent stem cells,ipsc,neuroinflammation,microglia,astrocytes,monoculture,co-culture,neural organoids,xenotransplantation,cytokines

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