3D Bioprinted Neural-Like Tissue as a Platform to Study Neurotropism of Mouse-Adapted SARS-CoV-2

Author(s):Show less -

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 ; Santana, Luiz C. ; Duraes-Carvalho, Ricardo ; Diaz, Ricardo S. ; Janini, Luiz M. R. ; Maricato, Juliana T. ; Porcionatto, Marimelia A.

• Document type: Journal article
• Source: ADVANCED BIOLOGY; v. 6, n. 8, p. 16-pg., 2022-05-06.

Abstract

The effects of neuroinvasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) become clinically relevant due to the numerous neurological symptoms observed in Corona Virus Disease 2019 (COVID-19) patients during infection and post-COVID syndrome or long COVID. This study reports the biofabrication of a 3D bioprinted neural-like tissue as a proof-of-concept platform for a more representative study of SARS-CoV-2 brain infection. Bioink is optimized regarding its biophysical properties and is mixed with murine neural cells to construct a 3D model of COVID-19 infection. Aiming to increase the specificity to murine cells, SARS-CoV-2 is mouse-adapted (MA-SARS-CoV-2) in vitro, in a protocol first reported here. MA-SARS-CoV-2 reveals mutations located at the Orf1a and Orf3a domains and is evolutionarily closer to the original Wuhan SARS-CoV-2 strain than SARS-CoV-2 used for adaptation. Remarkably, MA-SARS-CoV-2 shows high specificity to murine cells, which present distinct responses when cultured in 2D and 3D systems, regarding cell morphology, neuroinflammation, and virus titration. MA-SARS-CoV-2 represents a valuable tool in studies using animal models, and the 3D neural-like tissue serves as a powerful in vitro platform for modeling brain infection, contributing to the development of antivirals and new treatments for COVID-19. (AU)

• FAPESP's process: 21/03684-4 - Bats: epidemiological surveillance, high-resolution phylodynamics, search and design of peptides of biotechnological interest in emergent and reemerging viruses
• Grantee: Ricardo Durães de Carvalho
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 20/05289-2 - In vitro and in silico modeling of COVID-19
• Grantee: Marimélia Aparecida Porcionatto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/23039-3 - 3D Bioprinting of neural stem cells aiming the fabrication of neurogenic niches for the study of neurodegenerative diseases treatment
• Grantee: Bruna Alice Gomes de Melo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/01255-9 - Bats: epidemiological surveillance, high-resolution phylodynamics, search and design of peptides of biotechnological interest in emergent and reemerging viruses
• Grantee: Ricardo Durães de Carvalho
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system
• Grantee: Marimélia Aparecida Porcionatto
• Support Opportunities: Research Projects - Thematic Grants