Autor(es)

Feltran, Georgia da Silva ; da Silva, Rodrigo Augusto ; Fernandes, Celio Junior da Costa ; Ferreira, Marcel Rodrigues ; dos Santos, Sergio Alexandre Alcantara ; Justulin Jr, Luis Antonio ; Sosa, Liliana del Valle ; Zambuzzi, Willian Fernando

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 440, n. 2, p. 9-pg., 2024-07-02.

Resumo

Considering the importance of alternative methodologies to animal experimentation, we propose an organoidbased biological model for in vitro blood vessel generation, achieved through co -culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (alpha-SMA + cells) at the periphery and endothelial cells (CD31 + cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1 alpha expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1 alpha to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1 alpha. (AU)

• Processo FAPESP: 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/20505-8 - Geração e caracterização de esferoides de tecido endotelial e seu potencial osteopromotor
• Beneficiário: Geórgia da Silva Feltran
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/18785-8 - Fenótipo osteogênico induzido pelo endotélio: lições da análise ultra-estrutural de tecido equivalente
• Beneficiário: Geórgia da Silva Feltran
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Mestrado