Biology subjects

Claeyssens, F.

Publications and source records attributed to Claeyssens, F..

3 recordsLinked to original sources

bioRxiv2025

Alternate VEGFA isoform expression in fibrosarcoma leads to plasticity in cellular migration and differences in sensitivity to inhibition with anti-VEGFA antibodies

Metastasis remains a primary contributor to cancer-related mortality. Elevated expression of soluble vascular endothelial growth factor A (VEGFA) isoforms is linked to increased metastatic potential and enhanced cellular plasticity in response to microenvironmental changes. To investigate the connection between VEGFA isoform expression, migration plasticity, and metastasis, we analyzed the migratory behavior of fibrosarcoma cells expressing single VEGFA isoforms within engineered microenvironments mimicking tumor-associated extracellular matrix (ECM) architectures that drive distinct migration modes. Fibrosarcoma cell lines expressing VEGFA120 or VEGFA188 were derived from embryonic (Fs120 and Fs188) or mature skin fibroblasts, ensuring comparable VEGFA isoform expression across cells of different origins. Characterization of collagen fibril diameter and organization in tumors derived from Fs120 or Fs188 cells showed that Fs120 tumors had a higher degree of fibril alignment, suggesting VEGFA120 expression may facilitate ECM remodeling to support metastasis. To simulate these different collagen fibril structures for use in migration studies in vitro, we developed 3D platforms representing aligned and randomly organized collagen fibers using electrospinning of polycaprolactone. On 2D surfaces favoring mesenchymal migration and on 3D electrospun scaffolds promoting contact-guided migration, VEGFA120- and VEGFA188-expressing cells exhibited similar migratory capacities, regardless of their origin. However, anti-VEGFA antibodies selectively inhibited the migration of VEGFA120-expressing cells on fibronectin-coated surfaces and on aligned fiber scaffolds, but not non-aligned fibers, revealing isoform-specific sensitivity to VEGFA inhibition. In conclusion, while the expression of single VEGFA isoforms does not directly alter migration plasticity, VEGFA120 expression in mouse fibrosarcomas uniquely promotes ECM reorganization in tumors and cells expressing VEGF120 show increased sensitivity to anti-VEGFA antibodies.

cancer biology↗

bioRxiv2025

Angiogenic PolyHIPE Scaffolds Decorated with Extracellular Matrix as Periosteum Substitutes

1.The periosteum is the connective tissue that envelopes bone and contributes to the normal bone healing process. Periosteal grafts have shown excellent success in the treatment of nonunion bone defects but surgical challenges such as donor site morbidity and graft availability have limited their clinical use. Artificial periosteal membranes are being explored as off-the-shelf alternatives, with several groups investigating the use of decellularized tissues or extracellular matrix (ECM)-based strategies for this purpose. In this study, we investigate the use of in vitro-generated, fibroblast-derived ECM to decorate porous biodegradable scaffolds for use as synthetic periosteal grafts. Scaffolds were fabricated using an emulsion templating technique from a blend of polycaprolactone methacrylate (PCL-M) and poly(glycerol sebacate) methacrylate (PGS-M), resulting in membranes with large, interconnected pores (average pore size = 49.6 {+/-} 40.9 {micro}m, average window size = 12.6 {+/-} 6.1 {micro}m) and structural characteristics suitable for soft tissue applications. The BJ5ta fibroblast cell line was cultured on scaffolds for 14 days to deposit ECM, after which constructs were decellularized. When tested in vitro, periosteal-typical cells exhibited a significantly higher growth rate on ECM-decorated scaffolds compared to controls. Additionally, the chick chorioallantoic membrane (CAM) demonstrated that ECM decoration had a positive angiogenic effect. This proof-of-concept study highlights a promising approach to enhance the biological properties of synthetic membranes, while avoiding challenges associated with decellularizing whole tissues.

bioengineering↗

bioRxiv2022

Dynamic Compartmentalisation of Intracellular Sodium in collecting duct cells

In Principal cells (PC) of the cortical collecting duct (CCD), the highly regulated and coordinated reabsorption of sodium occurs through the epithelial sodium channel (ENaC) at the apical membrane and Na/K ATPase at the basolateral membrane. However, it is not known how sodium ions (Na+) are transported across the cell. We investigated intracellular transport in mCCDcl1 cells using a fluorescent sodium dye, CoroNa Green AM. Dye uptake was stimulated by aldosterone, blocked by amiloride (an ENaC inhibiter), and basolateral transport was prevented by ouabain (an Na/K ATPase blocker) thus validating the dyes apparently faithful replication of sodium transport. Cells exhibited a consistent pattern of sodium-containing vesicles, of various sizes, surrounded by cytoskeleton and lipid membrane. While the smallest vesicles ([~]0.5m) co-stained with lysotracker, larger vesicles (up to 6.4m) did not co-stain with either lysosomal- or mitochondrial-specific dyes and appeared to have internal structure, suggesting that they were multivesicular bodies. Time-lapse imaging showed a subset of these multivesicular bodies release or take up sodium dye in a controlled manner. Our novel data suggest that intracellular sodium compartmentalisation is highly regulated and offer new insights into intracellular sodium dynamics in the collecting duct, revealing potential new targets for control of sodium homeostasis. New and NoteworthyThe article shows for the first time, to our knowledge, intracellular sodium transport mechanism in mCCDcl1 cells in the form of dynamic vesicular bodies. These structures offer new targets for the regulation of sodium homeostasis and transport in the kidney collecting duct, with wider implications for blood pressure regulation.

cell biology↗