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Biology subjects

Thiebes, A. L.

Publications and source records attributed to Thiebes, A. L..

3 recordsLinked to original sources

The biomolecular profiles of extracellular vesicles from odontogenic stem cell lines depict donor-dependent differences and emphasize their therapeutic and regenerative potential

BackgroundStem cell-derived extracellular vesicles (EVs) hold great promise in regenerative medicine. However, a comprehensive understanding of the regenerative capabilities of EVs from different stem cell sources remains limited. MethodsThis study systematically compares EVs derived from three odontogenic cell types. Analyses includes EV isolation and characterization, cell viability assays, vasculogenesis experiments, proteomic profiling, and miRNA sequencing. ResultsAll three EV types displayed similar surface marker profiles. Dental pulp stem cell-derived EVs showed superior cellular uptake, promoted higher cell proliferation, and enhanced vasculogenesis compared to periodontal ligament stem cell-derived EVs. Gingival fibroblast-derived EVs performed similarly in functional assays. Principal component analysis of miRNA profiles revealed strong biological heterogeneity among EV sources, with donor-specific factors exerting a greater influence on EV characteristics than cellular origin--an aspect underexplored in prior studies. ConclusionsThese findings underscore the complexity of EV functionality and highlight the regenerative potential of dental stem cell-derived EVs.

cell biology↗

Differential behavior of pericytes and adipose stromal cells in vasculogenesis and angiogenesis

The pericyte is a key player in vascularization, protecting endothelial cells from external harm and promoting formation of new vessels and connections when necessary. However, pericytic identity and its relation with other cell types, such as the mesenchymal stromal/stem cells, is highly debated. To compare the behaviour of pericytes and unselected stromal cells in vascularization, we used multichannel microfluidic chips to replicate the two processes of vessel formation: vasculogenesis, the de novo vessel formation, and angiogenesis, the sprouting of new vessels from existing ones. In angiogenesis, pericytes promote significantly more and longer sproutings than stromal cells. In vasculogenesis, stromal cells promote the formation of structures ressembling the embryonic capillary plexus, whereas pericytes wrap around the endothelial cells, arresting their division and forcing them into tubulogenesis. Whole-transcriptome sequencing confirms an upregulation of pro-vascularization and cytostatic genes in co-cultures of pericytes and endothelial cells; while stromal cells strongly stimulate mitosis and organelle biogenesis pathways and decrease the release of pro-inflammatory cytokines. In this study, we offer new insights into the pericyte-endothelial cell relation and the mesenchymal stromal cell elusive identity, relevant in both vascular biology and tissue engineering.

cell biology↗

Towards Biohybrid Lung Development? Inflammatory Conditions Disrupt Endothelial Layer Integrity on Gas Exchange Membranes

Systemic inflammation presents a significant challenge to the long-term function of biohybrid implants. While endothelialisation of biohybrid implants has been shown to improve device hemocompatibility, its feasibility under the influence of patients inflammatory status remains largely unexplored. To investigate this, we developed a controlled in vitro model which allows to study endothelial dysfunction under inflammatory stress. Endothelial cells were cultured on polydimethylsiloxane under physiological shear stress and exposed to lipopolysaccharide (LPS)-activated peripheral blood mononuclear cells (PBMCs), simulating inflammatory conditions. Endothelial morphology and confluence was assessed using immunohistochemistry and scanning electron microscopy. Leukocyte adhesion was evaluated directly as well as indirectly, using flow cytometry to analyse cell adhesion molecules. Quantitative PCR was used for gene expression analysis of inflammatory mediators. Notably, neither LPS nor PBMCs alone induced endothelial disruption, whereas their combination significantly impaired endothelial confluence: Inflammatory activation led to substantial loss of endothelial confluence, increased leukocyte adhesion, and elevated expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin. Gene expression analysis highlights the upregulation of inflammatory mediators, such as IL-6, IL-8, IL-10, and MCP-1. This study underscores the challenges of implementing endothelialisation in biohybrid devices, particularly in patients with systemic inflammation. By considering translational hurdles, this work contributes to the development of clinically viable biohybrid constructs and highlights the importance of considering inflammatory dynamics when designing next-generation implants.

bioengineering↗