Biology subjects

Quintard, C.

Publications and source records attributed to Quintard, C..

3 recordsLinked to original sources

bioRxiv2024

Fusion of blood vessel organoids with human pancreatic islets improves insulin response over time.

Pancreatic islet transplantation is a promising treatment strategy for type 1 diabetes, however there are still major challenges to overcome, including vascularization. Novel strategies for the generation of prevascularized islets with native microvessels have reported improved islet functionality, vascularization and engraftment emphasizing integral role of microvascular bed. Recently a new model of self-organizing three-dimensional human blood vessel organoids (BVOs) has been developed from human pluripotent stem cells (hPSCs), composed of both endothelial and mural cells. BVO recapitulate key features of human microvasculature such as formation of vascular network, vascular lumen and basement membrane, and have been shown to be perfusable. Here, we report a new strategy to construct prevascularized islets by fusion with hPSC-derived BVOs. We demonstrate that islets and BVOs in co-culture leads to fusion and improved insulin secretion over time, on two independent human islet donors, suggesting a new therapeutic approach for pancreatic islet transplantation and type 1 diabetes modeling.

bioengineering↗

bioRxiv2021

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↗

bioRxiv2021

Microfluidic device integrating a network of hyper-elastic valves for automated glucose stimulation and insulin secretion collection from a single pancreatic islet

Advances in microphysiological systems have prompted the need for robust and reliable cell culture devices. While microfluidic technology has made significant progress, devices often lack user-friendliness and are not designed to be industrialized on a large scale. Pancreatic islets are often being studied using microfluidic platforms in which the monitoring of fluxes is generally very limited, especially because the integration of valves to direct the flow is difficult to achieve. Considering these constraints, we present a thermoplastic manufactured microfluidic chip with an automated control of fluxes for the stimulation and secretion collection of pancreatic islet. The islet was directed toward precise locations through passive hydrodynamic trapping and both dynamic glucose stimulation and insulin harvesting were done automatically via a network of large deformation valves, directing the reagents and the pancreatic islet toward different pathways. This device we developed enables monitoring of insulin secretion from a single islet and can be adapted for the study of a wide variety of biological tissues and secretomes.

bioengineering↗