Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system

• Grant number: 18/12605-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2019
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Marimélia Aparecida Porcionatto
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais:( Atuais ): Lucimara Gaziola de la Torre
• Pesquisadores principais:( Anteriores ): Paulo Schor
• Associated researchers: Alexander Birbrair ; Alexander Henning Ulrich ; Ana Luíza Garcia Millás Massaguer ; Andréa Laurato Sertié ; Angelo Luiz Gobbi ; Beatriz de Oliveira Monteiro ; Cristina Pacheco Soares ; Eduardo Henrique Backes ; Giselle Zenker Justo ; Isaias Glezer ; Jean Faber Ferreira de Abreu ; Kil Sun Lee ; Laura Lopez Mascaraque ; Laura Nicoleti Zamproni ; Lucimara Gaziola de la Torre ; Luiz Eugenio Araujo de Moraes Mello ; Paulo Schor ; Renato Sousa Lima ; Sang Won Han ; Su Ryon Shin
• Associated research grant(s): 24/19239-8 - Contribution of APOE genotypes to blood-brain barrier permeability in Alzheimer's disease, AP.R SPRINT; 20/05289-2 - In vitro and in silico modeling of COVID-19, AP.R
• Associated scholarship(s): 24/04078-9 - Prohibitins in sporadic Alzheimer's disease: function and potential drug target, BP.DR; 24/12270-7 - Application of a 3D model for studying cortical neurogenesis and the WNT pathway using hiPSCs from a patient with autism spectrum disorder and macrocephaly, BP.DD; 24/15729-0 - Electrophysiological correlates of ASD in hiPSC-derived bioprinted neural constructs, BP.PD; + associated scholarships 24/02561-4 - Effects of circadian oscillation on the role of astrocytes as supplier of active thyroid hormone, BP.IC; 24/00599-4 - Alzheimer's disease: scientific dissemination actions for non-specialized audiences, BP.JC; 24/00610-8 - Alzheimer's disease: scientific dissemination actions for non-specialized audiences, BP.JC; 23/14105-0 - Identification of chemotactic factors responsible for the migratory control of hiPSCs-NPC cells in a 3D bioprinted model, BP.DR; 22/16677-9 - 3D bioprinting of hiPSC-derived neuroprogenitor cells as a model for studying neurogenesis, BP.MS; 22/16690-5 - Synthetic biology associated with nanotechnology: obtaining transmembrane proteins for the production of biomimetic nanovesicles by microfluidic process, BP.DD; 23/09081-5 - In vitro modeling of the blood-brain barrier for studies of late-onset Alzheimer's Disease, BP.PD; 23/08210-6 - Action of advanced glycation end products on the blood-brain barrier and its relationship with Alzheimer's disease, BP.IC; 23/08040-3 - Bioprinting of murine neurospheres in an amyloid beta microenvironment, BP.IC; 23/08072-2 - In vitro modeling of sporadic Alzheimer's disease associated with hyperglycemia, BP.IC; 22/04258-1 - Exploring neurovascular unit adaptations in the regulation of apoptosis and glial response after brain injury, BP.PD; 22/16047-5 - Development of 3D biopatches containing neuroprogenitors for repair of central nervous system lesions, BP.IC; 22/16448-0 - Study of fatty acids transport across the blood brain barrier in iron deficiency condition., BP.IC; 23/00081-2 - 3D bioprinting of neural stem cells to mimic neurogenic niches, BP.TT; 22/15909-3 - Use of biomateriomics approaches to identify, characterize and validate biomaterials for the production of synthetic neural tissues, BP.PD; 22/08664-4 - 3D bioprinting of vascular structures to model and study the role of the neurovascular unit in Stroke and Alzheimer's Disease, BP.PD; 21/14327-8 - Subarachnoid haemorrhage-in-a-chip, BP.PD; 21/07024-9 - Evaluation of the use of neuroblastoma cell line Neuro2a as a study model for inhibition of axonal growth in 2D and 3D, BP.IC; 21/10787-4 - Study of the synergy between PROK2 and CXCL12 in the chemotaxis of neuroblasts and endothelial cells in bioprinted tissue, BP.IC; 20/12454-0 - 3D bioprinting of reactive astrocyte-derived neural stem cells, BP.DR; 21/02795-7 - Brain-on-a-chip microfluidic platform for mimicking the blood-brain barrier, BP.DD; 20/07402-0 - 3D bioprinted model of the blood-brain-barries to study the development of Alzheimer´s s disease, BP.IC - associated scholarships

Abstract

The concept of organ-on-a-chip refers to different types of in vitro modeling or reproduction of tissues and organs by combining cells and biocompatible material. This approach has become an attractive alternative for various studies, such as drug testing. The initial push was the worldwide effort to reduce the number of lab animals used in research, by the application of the 3R's - replacement, reduction, and refinement, although organs-on-a-chip have proven to have broader applications, such as the study organ development and drug testing. Microplataforms to model the central nervous system (CNS), known as brain-on-a-chip, have also been developed, as a combination of neural stem cells or induced pluripotency stem cells (iPSCs) cultured on biocompatible materials with the introduction of microfluidic chambers to mimic blood flow and the blood-brain-barrier, and the cerebrospinal fluid. Brain-on-a-chip microplataforms used for in vitro studies of the CNS allow several different applications such as drug testing and the study of cellular and molecular mechanisms of neurodegenerative diseases. In this scenario, our goal is to develop microplataforms to study CNS normal development, cellular and molecular mechanisms of disorders of the CNS, and neuronal connectivity, using 3D bioprinting, microfluidic chambers and microelectrode arrays (MEAs). (AU)

Scientific publications

(13)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, NATALIA DALL'AGNOL; FERREIRA, PAULA SCANAVEZ; SOARES, CRISTINA PACHECO; PORCIONATTO, MARIMELIA APARECIDA; SALLES, GEISA RODRIGUES. 3D-bioprinted model of adult neural stem cell microenvironment in Alzheimer's disease. INTERNATIONAL JOURNAL OF BIOPRINTING, v. 10, n. 5, p. 24-pg., 2024-01-01. (18/12605-8, 23/08040-3, 22/08664-4)

DE MELO, BRUNA A. G.; MUNDIM, MAYARA, V; LEMES, ROBERTHA M. R.; CRUZ, ELISA M.; RIBEIRO, TAIS N.; SANTIAGO, CAROLINA F.; DA FONSECA, JESSICA H. L.; BENINCASA, JULIA C.; STILHANO, ROBERTA S.; MANTOVANI, NATHALIA; et al. 3D Bioprinted Neural-Like Tissue as a Platform to Study Neurotropism of Mouse-Adapted SARS-CoV-2. ADVANCED BIOLOGY, v. 6, n. 8, p. 16-pg., 2022-05-06. (21/03684-4, 20/05289-2, 18/23039-3, 19/01255-9, 18/12605-8)

ZAMPRONI, LAURA N.; MUNDIM, MAYARA T. V. V.; PORCIONATTO, MARIMELIA A.. Neurorepair and Regeneration of the Brain: A Decade of Bioscaffolds and Engineered Microtissue. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 09, p. 16-pg., 2021-04-07. (14/00927-0, 14/23797-4, 18/12605-8, 13/16533-8, 12/06810-1)

MAROZZI CRUZ, E.; PORCIONATTO, M. A.. Activation of the neurogenic potential in 3D bioprinted astrocytes. Glia, v. 71, p. 1-pg., 2023-07-01. (20/12454-0, 18/12605-8, 22/06554-7)

DE MELO, BRUNA A. G.; JODAT, YASAMIN A.; CRUZ, ELISA M.; BENINCASA, JULIA C.; SHIN, SU RYON; PORCIONATTO, MARIMELIA A.. Strategies to use fibrinogen as bioink for 3D bioprinting fibrin-based soft and hard tissues. Acta Biomaterialia, v. 117, p. 60-76, NOV 2020. (18/23039-3, 18/12605-8)

RIBEIRO, TAIS NOVAKI; DELGADO-GARCIA, LINA MARIA; PORCIONATTO, MARIMELIA A.. Notch1 and Galectin-3 Modulate Cortical Reactive Astrocyte Response After Brain Injury. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, JUN 16 2021. (16/25737-4, 18/05846-9, 16/19084-8, 18/12605-8, 15/19231-8)

ANTONELLO, PRISCILA C.; VARLEY, THOMAS F.; BEGGS, JOHN; PORCIONATTO, MARIMELIA; SPORNS, OLAF; FABER, JEAN. Self-organization of in vitro neuronal assemblies drives to complex network topology. eLIFE, v. 11, p. 29-pg., 2022-06-16. (18/12605-8)

ZAMPRONI, LAURA N.; MUNDIM, MAYARA T. V. V.; PORCIONATTO, MARIMELIA A.. eurorepair and Regeneration of the Brain: A Decade of Bioscaffolds and Engineered Microtissu. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 09, APR 7 2021. (18/12605-8, 12/06810-1, 14/00927-0, 14/23797-4, 13/16533-8)

CRUZ, ELISA MAROZZI; MACHADO, LUCAS SIMOES; ZAMPRONI, LAURA NICOLETI; BIM, LARISSA VALDEMARIN; FERREIRA, PAULA SCANAVEZ; PINTO, LEONARDO ALVES; PESSAN, LUIZ ANTONIO; BACKES, EDUARDO HENRIQUE; PORCIONATTO, MARIMELIA APARECIDA. A Gelatin Methacrylate-Based Hydrogel as a Potential Bioink for 3D Bioprinting and Neuronal Differentiation. PHARMACEUTICS, v. 15, n. 2, p. 22-pg., 2023-02-01. (18/12605-8, 20/12454-0, 20/11374-2, 19/27415-2, 21/14327-8)

SALLES, GEISA RODRIGUES; GRANATO, ALESSANDRO E. C.; VIERO, FERNANDA TIBOLLA; PACHECO-SOARES, CRISTINA; FERREIRA, SERGIO T.; PORCIONATTO, MARIMELIA; ULRICH, HENNING. Self-assembly and 3D Bioprinting of Neurospheres and Evaluation of Caffeine and Photobiomodulation Effects in an Alzheimer's Disease In Vitro Model. STEM CELL REVIEWS AND REPORTS, v. N/A, p. 13-pg., 2025-04-08. (22/08664-4, 18/12605-8)

DELGADO-GARCIA, LINA M.; OJALVO-SANZ, ANA C.; NAKAMURA, THABATTA K. E.; MARTIN-LOPEZ, EDUARDO; PORCIONATTO, MARIMELIA; LOPEZ-MASCARAQUE, LAURA. Dissecting reactive astrocyte responses: lineage tracing and morphology-based clustering. Biological Research, v. 57, n. 1, p. 16-pg., 2024-08-14. (19/09183-7, 16/19084-8, 18/12605-8, 22/04258-1)

MELLO DA LUZ, MARCIO HENRIQUE; VOLEJNIK PINO, JESSICA MONTEIRO; MONICO-NETO, MARCOS; DE AMORIM, PRISCILA NICOLICHT; MOREIRA ANTUNES, HANNA KAREN; PORCIONATTO, MARIMELIA APARECIDA; LEE, KIL SUN. Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs Aβ clearance in hippocampus of rats. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1869, n. 6, p. 12-pg., 2023-08-01. (18/12605-8, 16/04297-6, 17/10404-2, 19/21511-0)

DE MELO, BRUNA A. G.; CRUZ, ELISA M.; RIBEIRO, TAIS N.; MUNDIM, V, MAYARA; PORCIONATTO, MARIMELIA A.. 3D Bioprinting of Murine Cortical Astrocytes for Engineering Neural-Like Tissue. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 173, JUL 2021. (18/23039-3, 18/12605-8)