| Texto completo | |
| Autor(es): |
Machado, Lucas Simoes
;
Ferreira, Paula Scanavez
;
Pires, Marina Rodrigues
;
Bim, Larissa Valdemarin
;
de Oliveira, Natalia Heloisa
;
Salles, Geisa Rodrigues
;
Ferreira, Natalia Dall'Agnol
;
Cruz, Elisa Marozzi
;
Porcionatto, Marimelia Aparecida
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | APL BIOENGINEERING; v. 9, n. 3, p. 18-pg., 2025-09-01. |
| Resumo | |
Animal 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 Geltrex (TM)/GelMA hydrogel blend to bioprint human induced pluripotent stem cells-derived NPCs (hNPCs). We show that 3D bioprinted hNPCs can self-organize, 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 TUBB3+ 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. (C) 2025 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND) license (https://creativecommons.org/licenses/by-nc-nd/4.0/).https://doi.org/10.1063/5.0276704B (AU) | |
| Processo FAPESP: | 18/12605-8 - Desenvolvimento de microplataformas brain-on-a-chip para modelagem do sistema nervoso central in vitro |
| Beneficiário: | Marimélia Aparecida Porcionatto |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 19/08975-7 - EMU concedido no processo 2018/15539-6: reômetro modular compacto e acessórios |
| Beneficiário: | Fabiana Perrechil Bonsanto |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |