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

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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.

• Tipo de documento: Artigo Científico
• Fonte: ADVANCED BIOLOGY; v. 6, n. 8, p. 16-pg., 2022-05-06.

Resumo

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)

• Processo FAPESP: 21/03684-4 - Morcegos: vigilância epidemiológica, filodinâmica de alta resolução, busca e design de peptídeos de interesse biotecnológico em vírus emergentes e reemergentes
• Beneficiário: Ricardo Durães de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 20/05289-2 - Modelagem da COVID-19 in vitro e in silico
• Beneficiário: Marimélia Aparecida Porcionatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/23039-3 - Bioimpressão 3D de células-tronco neurais visando mimetizar nichos neurogênicos para estudos de doenças neurodegenerativas
• Beneficiário: Bruna Alice Gomes de Melo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/01255-9 - Morcegos: vigilância epidemiológica, filodinâmica de alta resolução, busca e design de peptídeos de interesse biotecnológico em vírus emergentes e reemergentes
• Beneficiário: Ricardo Durães de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• 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