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Biology subjects

Leopoldi, A.

Publications and source records attributed to Leopoldi, A..

2 recordsLinked to original sources

An automated microfluidic platform integrating functional vascularized organoids-on-chip

The development of vascular networks on-chip is crucial for the long-term culture of three-dimensional cell aggregates such as organoids, spheroids, tumoroids, and tissue explants. Despite the rapid advancement of microvascular network systems and organoid technology, vascularizing organoids-on-chips remains a challenge in tissue engineering. Moreover, most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical settings to operate. Considering these constraints, we developed an innovative platform to establish and monitor the formation of endothelial networks around model spheroids of mesenchymal and endothelial cells as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 15 days on-chip. Importantly, these networks were functional, demonstrating intravascular perfusion within the spheroids or vascular organoids connected to neighbouring endothelial beds. This microphysiological system thus represents a viable organ-on-chip model to vascularize biological tissues and should allow to establish perfusion into organoids using advanced microfluidics.

bioengineering↗

A diabetic milieu increases cellular susceptibility to SARS-CoV-2 infections in engineered human kidney organoids and diabetic patients

SARS-CoV-2 infections lead to a high risk of hospitalization and mortality in diabetic patients. Why diabetic individuals are more prone to develop severe COVID-19 remains unclear. Here, we established a novel human kidney organoid model that mimics early hallmarks of diabetic nephropathy. High oscillatory glucose exposure resulted in metabolic changes, expansion of extracellular membrane components, gene expression changes determined by scRNAseq, and marked upregulation of angiotensin-converting enzyme 2 (ACE2). Upon SARS-CoV-2 infection, hyperglycemic conditions lead to markedly higher viral loads in kidney organoids compared to normoglycemia. Genetic deletion of ACE2, but not of the candidate receptor BSG/CD147, in kidney organoids demonstrated the essential role of ACE2 in SARS-CoV-2 infections and completely prevented SARS-CoV-2 infection in the diabetogenic microenvironment. These data introduce a novel organoid model for diabetic kidney disease and show that diabetic-induced ACE2 licenses the diabetic kidney to enhanced SARS-CoV-2 replication.

cell biology↗