bioRxiv Science⌕ Search

Biology subjects

Pitaval, A.

Publications and source records attributed to Pitaval, A..

3 recordsLinked to original sources

Human decellularized extracellular matrix from adipose tissue is a permissive microenvironment for pancreatic organoids generation

In vitro reconstruction of human tissue microenvironments that integrate native biochemical and biomechanical cues is essential for disease modelling, regenerative medicine, and personalized therapeutic approaches. However, most currently available engineered matrices fail to recapitulate the complexity and tissue specificity of the human extracellular matrix (ECM). To address this limitation, we developed a novel hydrogel derived from decellularized human adipose tissue (atdECM) designed to support three-dimensional culture of human cells. The decellularization and delipidation processes were first validated, and the biochemical composition and biomechanical properties of atdECM were comprehensively characterized. Human pancreatic organoids were then cultured within atdECM hydrogel, and their structural organization and transcriptional profiles were analyzed and compared with those obtained in Matrigel, the current gold-standard matrix for organoid culture. Proteomic and cytokine analyses demonstrated efficient decellularization while preserving collagen-rich ECM architecture and a diverse repertoire of soluble bioactive factors. AtdECM exhibited physiological stiffness and retained tissue-specific extracellular cues. Pancreatic organoids cultured in atdECM displayed morphological similarities with those grown in Matrigel but exhibited transcriptional profiles more consistent with physiological epithelial homeostasis, with reduced activation of inflammatory and stress-related pathways. Altogether, these findings indicate that atdECM provides a human-derived, tissue-relevant, and permissive microenvironment for human organoid generation. This platform represents a promising alternative to Matrigel for studying human tissue biology and for developing physiologically relevant in vitro models.

bioengineering↗

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↗

Spatial integration of mechanical forces by alpha-actinin establishes actin network symmetry.

Cell and tissue morphogenesis depend on the production and spatial organization of tensional forces in the actin cytoskeleton. Actin network architecture is complex because it is made of distinct modules in which filaments adopt a variety of organizations. The assembly and dynamics of these modules is well described but the self-organisation rules directing the global network architecture are much less understood. Here we investigated the mechanism regulating the interplay between network architecture and the geometry of cells extracellular environment. We found that -actinin, a filament crosslinker, is essential for network symmetry to be consistent with extracellular microenvironment symmetry. It appeared to be required for the interconnection of transverse arcs with radial fibres to ensure an appropriate balance between forces at cell adhesions and across the entire actin network. Furthermore, the connectivity of the actin network appeared necessary for the cell ability to integrate and adapt to complex patterns of extracellular cues as they migrate. Altogether, our study has unveiled a role of actin-filament crosslinking in the physical integration of mechanical forces throughout the entire cell, and the role of this integration in the establishment and adaptation of intracellular symmetry axes in accordance with the geometry of extracellular cues.

cell biology↗