Bioprinting of murine neurospheres in an amyloid beta microenvironment

• Grant number: 23/08040-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: December 29, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Natalia Dall'Agnol Ferreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system, AP.TEM

Abstract

The primary pathophysiological mechanism involved in Alzheimer's disease (AD) is related to the extracellular formation of amyloid ² (A²) plaques. This change is highly neurotoxic, resulting in synaptic damage and increased oxidative stress, with a local inflammatory response followed by neuronal death. Neuroinflammation also inhibits neurogenesis, contributing to neural stem cell (NSCs) senescence, memory, and cognitive loss. In vivo and in vitro models are fundamental for understanding neurodegenerative pathologies, including AD, and, more recently, the development of new biomaterials has contributed to these studies. The combination of cells and biocompatible materials, in addition to minimizing the use of experimental animals, allows the in vitro simulation of the main pathogenic events of diseases. Thus, bioprinting and three-dimensional (3D) culture emerge as an alternative to mimic the 3D microenvironment of brain tissue and study cell-cell and cell-extracellular microenvironment interactions. This project aims to produce a 3D biomaterial mimicking the AD microenvironment through 3D bioprinting of constructs using bioink containing A² oligomers (A²Os) and neurospheres composed of NSCs, extracted from the neurogenic zones of wild-type (C57bl/6) and transgenic mice from DA (APP/PS1). The biomaterial will be developed, characterized, and standardized to be used as a bioink for 3D printing. Biological parameters will be evaluated, such as differentiation of NSCs in neurospheres, oxidative stress, senescence, and cell death. It is intended that the bioprinted constructs act as an in vitro model for the study of AD, simulating essential attributes of the disease.