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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        3D-bioprinted model of adult neural stem cell

                                        microenvironment in Alzheimer’s disease



                                        Natalia Dall’Agnol Ferreira 1,2 id , Paula Scanavez Ferreira 1,2 id ,
                                        Cristina Pacheco Soares 3 id , Marimelia Aparecida Porcionatto * ,
                                                                                             1,2 id
                                                                  *
                                        and Geisa Rodrigues Salles 1,2,3 id
                                        1  Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo,
                                        São Paulo, Brazil
                                        2  National Institute of Science and Technology in Modeling Human Complex Diseases with 3D
                                        Platforms (INCT Model 3D), São Paulo, Brazil
                                        3
                                         Research & Development Institute, Universidade do Vale do Paraíba, São José dos Campos, São
                                        Paulo, Brazil
                                        (This article belongs to the Special Issue: Innovative Tissue and Diseases Models – Novelties in Bioprinting/3D
                                        bioprinting)




                                        Abstract

                                        Neurogenesis  plays a major  role  in neuroplasticity  and memory. In  adult  human
                                        and mouse brains, neural stem cells (NSCs) are mainly distributed in two extensively
                                        characterized neurogenic niches: the subgranular zone (SGZ) of the hippocampus and
                                        the subventricular zone (SVZ) of the lateral ventricles. Impaired neurogenesis is one
            *Corresponding authors:     of the consequences of Alzheimer’s disease (AD), contributing to cognitive decline
            Marimelia Aparecida Porcionatto    and progressive memory loss. Developing new in vitro models that resemble this
            (marimelia.porcionatto@unifesp.br)  three-dimensional (3D) structure is fundamental for enhancing our understanding
            Geisa Rodrigues Salles      of the SVZ neurogenic niche dynamics in AD. Herein, we produced and characterized
            (geisa.salles@unifesp.br)
                                        a 3D-bioprinted model of the adult SVZ neurogenic niche containing amyloid β
            Citation: Ferreira NDA, Ferreira PS,  (Aβ) oligomers, mimicking the NSC microenvironment in AD. In this model, Aβ
            Soares CP, Porcionatto MA, Salles   oligomers induce oxidative stress and reduce the proliferative potential of NSCs,
            GR. 3D-bioprinted model of adult
            neural stem cell microenvironment   while stimulating neuronal differentiation. We hypothesize that these events are an
            in Alzheimer’s disease.     early attempt of adult NSCs to compensate for neuronal death in AD pathogenesis.
            Int J Bioprint. 2024;10(5):3751.    Our 3D model simulates the NSC niche physiology, reproducing an early response of
            doi: 10.36922/ijb.3751
                                        NSCs in AD, strengthening the importance of studying the potential of neurogenesis
            Received: May 24, 2024      in neurodegeneration.
            Accepted: July 19, 2024
            Published Online: September 13,
            2024
                                        Keywords: Bioprinting; Neurogenic niche; Alzheimer’s disease; Amyloid beta;
            Copyright: © 2024 Author(s).   Neural stem cells; Subventricular zone
            This is an Open Access article
            distributed under the terms of the
            Creative Commons Attribution
            License, permitting distribution,
            and reproduction in any medium,   1. Introduction
            provided the original work is
            properly cited.             Neurogenesis is defined as the process of generating neurons from neural stem cells
            Publisher’s Note: AccScience   (NSCs). In the adult brain, neurogenesis confers plasticity and neuronal replacement
            Publishing remains neutral with   and occurs primarily in specialized regions known as neurogenic niches. The two main
            regard to jurisdictional claims in
            published maps and institutional   neurogenic niches of human and mouse brains are located in the subgranular zone
            affiliations.               (SGZ) of the hippocampus and the subventricular zone (SVZ) of lateral ventricles. As


            Volume 10 Issue 5 (2024)                       502                                doi: 10.36922/ijb.3751
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