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Biology subjects

Grossemy, S. E.

Publications and source records attributed to Grossemy, S. E..

2 recordsLinked to original sources

Development of a Polyelectrolyte Complex Scaffold and its specific cell seeding method as a tool for liquid cancers drug screening

This study focuses on the development of 3D culture model dedicated to liquid cancers drug screening. The challenge addressed was to effectively retain non adherent small cells within a 3D-scaffold with tailorable mechanical properties, while proposing a fast and effective tool for drug screening. To that aim, we developed a macroporous alginate-chitosan polyelectrolyte complex (PEC) scaffold combined with a low-viscosity alginate (LVA) cell seeding solution. We hypothesized that LVA could undergo in situ pore gelation via calcium ions retained from the PEC fabrication process, enabling effective retention and homogeneous cell distribution, leading to an improved platform for drug screening and personalized medicine. First, we evaluated scaffold suitability for LVA infiltration and gelation. Microtomography revealed a highly porous architecture (98%) enabling LVA homogeneous penetration and complete gelation within 30 min, as confirmed by SEM, microscopy, rheology, and micro-rheology. Next, we assessed cell retention and biocompatibility using primary human chronic lymphocytic leukemia (CLL) cells. LVA-assisted seeding increased cell density 2.6-fold compared to medium alone, with homogeneous distribution, >80% viability over 7 days, and preserved differentiation into nurse-like cells. Finally, we demonstrated a proof of concept for drug screening. The Alginate-PEC scaffold (A-PEC scaffold) supported both qualitative live/dead imaging and rapid quantitative viability measurement with the Alamar Blue assay. Drug responses reproduced microenvironment-dependent protection effects observed in vivo. This integrated scaffold and seeding method provides a promising 3D platform for in vitro liquid cancer studies and drug screening on patient-derived hematological cancer cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/722037v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@9b71d4org.highwire.dtl.DTLVardef@14e1dd0org.highwire.dtl.DTLVardef@1876a56org.highwire.dtl.DTLVardef@15656bc_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Unravelling the distinct phenotype and mechanosensitive properties of different tendon cell populations.

Tendinopathy arises from maladaptive cellular responses, though the drivers remain unclear. Here we identify and characterise a previously undescribed tendon cell population residing within interfascicular matrix (IFM), demonstrating its importance as the primary mechanosensitive cell in tendon. We describe the first successful isolation and long-term culture of primary IFM and fascicular matrix (FM) cells, enabling direct comparison of their phenotypes and mechanosensitivity. IFM cells exhibited a potent response to stiff substrates, displaying cytoskeletal remodelling, rapid drifting of tenogenic and ECM gene expression, and proliferative decline, while FM cells remained largely unaltered. Crucially, transferring IFM cells to compliant, IFM-like substrates recovered their proliferative capacity, morphology, gene expression. This work defines IFM cells as the primary mechanosensitive tendon cell population, with implications for tendon ageing, injury, and regeneration. Importantly, it also enables identification of cell surface markers to isolate this population from other tendons, opening new avenues to explore mechanobiology-guided tendon therapeutics.

bioengineering↗