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TLR4-Mediated Neuroinflammation in Human Induced Pluripotent Stem Cells and Cerebral Organoids

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The Role of Toll-Like Receptor 4 in Infectious and Non Infectious Inflammation

Part of the book series: Progress in Inflammation Research ((PIR,volume 87))

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Abstract

The discovery of a reprogramming method to induce pluripotency in human somatic cells marked a dramatic turning point in the recent history of scientific progresses. Induced pluripotent stem cell (iPSCs) technology has been applied in regenerative and transplant medicine, disease modelling, drug screening, and studies on human developmental biology. The inflammatory responses elicited in healthy and diseased organisms have been extensively studied in animal models or artificial cell cultures, showing great usefulness but also some important limitations. Thus, the use of iPSCs as source of human cell cultures or organized tissues represented a great opportunity for neuroimmunology. In the latest years, the ability of iPSC-derived microglia to reproduce in vitro some of the genetic and phenotypic features of human adult microglia was shown. The development of platforms in which microglia, neurons, and macroglia derived from healthy or diseased subjects grow and mature in a single system allowed to demonstrate the role of toll-like receptor 4 (TLR4) in mediating neuroinflammation. The generation of three-dimensional (3D) microglia-embedded or -enriched organoids represent a dramatic further development of biologically relevant human-based models. In this context, the demonstrations of high similarity in gene expression and sensitivity to its endogenous and infective ligands in 3D constructs pose microglia-containing brain organoids in a prominent position for in-depth investigations on how TLR4 regulates immune cells interactions to orchestrate brain development and react to injury.

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Authors and Affiliations

  1. Department of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy

    Massimiliano De Paola

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  1. Massimiliano De Paola
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Correspondence to Massimiliano De Paola .

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Editors and Affiliations

  1. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Carlo Rossetti

  2. Department of Biotechnology and Biosciences, University of Milano Bicocca, Milan, Italy

    Francesco Peri

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De Paola, M. (2021). TLR4-Mediated Neuroinflammation in Human Induced Pluripotent Stem Cells and Cerebral Organoids. In: Rossetti, C., Peri, F. (eds) The Role of Toll-Like Receptor 4 in Infectious and Non Infectious Inflammation. Progress in Inflammation Research, vol 87. Springer, Cham. https://doi.org/10.1007/978-3-030-56319-6_8

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