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Differentiation of Neurons, Astrocytes, Oligodendrocytes and Microglia From Human Induced Pluripotent Stem Cells to Form Neural Tissue-On-Chip: A Neuroinflammation Model to Evaluate the Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells

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Abstract

Advances in stem cell (SC) technology allow the generation of cellular models that recapitulate the histological, molecular and physiological properties of humanized in vitro three dimensional (3D) models, as well as production of cell-derived therapeutics such as extracellular vesicles (EVs). Improvements in organ-on-chip platforms and human induced pluripotent stem cells (hiPSCs) derived neural/glial cells provide unprecedented systems for studying 3D personalized neural tissue modeling with easy setup and fast output. Here, we highlight the key points in differentiation procedures for neurons, astrocytes, oligodendrocytes and microglia from single origin hiPSCs. Additionally, we present a well-defined humanized neural tissue-on-chip model composed of differentiated cells with the same genetic backgrounds, as well as the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles to propose a novel treatment for neuroinflammation derived diseases. Around 100 nm CD9 + EVs promote a more anti-inflammatory and pro-remodeling of cell–cell interaction cytokine responses on tumor necrosis factor-α (TNF-α) induced neuroinflammation in neural tissue-on-chip model which is ideal for modeling authentic neural-glial patho-physiology.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Financial support provided by The Scientific and Technological Research Council of Turkey (TUBITAK) under grant number 119M578 is highly appreciated. P.S-M. gratefully acknowledges the TUBITAK 2211-A National Graduate Scholarship Program and 2214-A International Doctoral Research Fellowship Program. E.D. acknowledges 2210-C National Graduate Scholarship Program. We also acknowledge Finnadvance Company for providing microfluidic chip platforms.

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Authors and Affiliations

  1. Department of Bioengineering, Faculty of Engineering, Ege University, Izmir, Turkey

    Pelin Saglam-Metiner, Elif Duran & Ozlem Yesil-Celiktas

  2. Department of Translational Neuroscience, Division of Neuroscience, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Pelin Saglam-Metiner

  3. Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey

    Leila Sabour-Takanlou & Cigir Biray-Avci

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Conceptualization: P.S-M., E.D. and O.Y-C.; Writing – Original Draft Preparation: P.S-M., E.D. and L.S.; Writing – Review & Editing: C.B-A., O.Y.C. and also P.S-M.; Supervision and Funding Acquisition: O.Y-C. All authors have read and agreed to the published version of the manuscript.

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Saglam-Metiner, P., Duran, E., Sabour-Takanlou, L. et al. Differentiation of Neurons, Astrocytes, Oligodendrocytes and Microglia From Human Induced Pluripotent Stem Cells to Form Neural Tissue-On-Chip: A Neuroinflammation Model to Evaluate the Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells. Stem Cell Rev and Rep 20, 413–436 (2024). https://doi.org/10.1007/s12015-023-10645-8

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