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Item 3D-bioprinted model of adult neural stem cell microenvironment in Alzheimer’s disease(ACCSCIENCE Publishing) Ferreira, Natalia Dall’Agnol; Ferreira, Paula Scanavez; Soares, Cristina Pacheco; Porcionatto, Marimelia Aparecida; Salles, Geisa RodriguesNeurogenesis 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 of the consequences of Alzheimer’s disease (AD), contributing to cognitive decline and progressive memory loss. Developing new in vitro models that resemble this three-dimensional (3D) structure is fundamental for enhancing our understanding of the SVZ neurogenic niche dynamics in AD. Herein, we produced and characterized a 3D-bioprinted model of the adult SVZ neurogenic niche containing amyloid β (Aβ) oligomers, mimicking the NSC microenvironment in AD. In this model, Aβ oligomers induce oxidative stress and reduce the proliferative potential of NSCs, while stimulating neuronal differentiation. We hypothesize that these events are an early attempt of adult NSCs to compensate for neuronal death in AD pathogenesis. Our 3D model simulates the NSC niche physiology, reproducing an early response of NSCs in AD, strengthening the importance of studying the potential of neurogenesis in neurodegeneration.Item 3D bioprinted human iPSC-derived neural progenitor cells as a novel platform for studying neurogenic niche(AIP Publishing) Machado, Lucas Simões; Ferreira, Paula Scanavez; Pires, Marina Rodrigues; Bim, Larissa Valdemarin; Oliveira, Natália Heloísa de; Salles, Geisa Rodrigues; Ferreira, Natalia Dall'Agnol; Cruz, Elisa Marozzi; Porcionatto, Marimelia AparecidaAnimal models, especially rodents, used to study neurodevelopment have significantly advanced our comprehension of cellular and molecular mechanisms. Nevertheless, differences in species-specific structures, gestation periods, and interneuronal connections limit animal models’ ability to represent human neurodevelopment accurately. The unique characteristics of primate neural progenitor cells (NPCs) enable cortex expansion with gyrus formation, which does not occur in lissencephalic animals, like rodents. Therefore, there is a need for novel in vitro models using human cells that recapitulate the complexity of human brain development. Along with organoids, 3D bioprinting offers a platform for creating more complex in vitro models. We developed, extensively characterized, and successfully used a GeltrexTM/GelMA hydrogel blend to bioprint human induced pluripotent stem cells-derived NPCs (hNPCs). We show that 3D bioprinted hNPCs can selforganize, revealing key features of a neurogenic niche, including proliferation, differentiation, and migration, remaining viable for over 110 days. Within the first 20 days, bioprinted constructs showed the formation of positive cell clusters for the neurogenic niche cell markers FABP7, NESTIN, and GFAP. Clusters were interconnected by process bundles supporting cell migration. The cells proliferated within the clusters, and over time, NPCs originated TUBB3þ neurons with long axonal tracts, prominent around the clusters. We propose this as a 4D model to study neurogenic niches’ key cellular and molecular features in a 3D bioprinted scaffold, adding time as the fourth dimension. Neuronal maturation in this dynamic model recapitulates key neurogenic niche properties, making it suitable for neurodevelopmental disease modeling and drug screening.