Circulating tumor cells shed large extracellular vesicles in capillary-sized bifurcations.

Circulating tumor cells (CTCs) and their clusters are the drivers of metastasis, but their interactions with capillary beds are poorly understood. Using microfluidic models mimicking human capillary bifurcations, we observed cell size- and bifurcation-dependent shedding of nuclei-free fragments by patient CTCs, CTC-derived explant cells and numerous cancer cell lines. Shedding reduced cell sizes up to 61%, facilitating their transit through bifurcations. We demonstrated that shed fragments were a novel class of large extracellular vesicles (LEVs), whose proteome was associated with immune-related and signaling pathways. LEVs were internalized by endothelial and immune cells, disrupted endothelial barrier integrity and polarized monocytes into M2 tumor-promoting macrophages. Cumulatively, these findings suggest that CTCs shed LEVs in capillary beds that drive key processes involved in the formation of pre-metastatic niches.

Human Hair Keratin-Based Hydrogels in Regenerative Medicine: Current Status and Future Directions.

Regenerative medicine (RM) is a multidisciplinary field that utilizes the inherent regenerative potential of human cells to generate functionally and physiologically acceptable human cells, tissues, and organs in vivo or ex vivo. An appropriate biomaterial scaffold with desired physicochemical properties constitutes an important component of a successful RM approach. Among various forms of biomaterials explored until the present day, hydrogels have emerged as a versatile candidate for tissue engineering and regenerative medicine (TERM) applications such as scaffolds for spatial patterning and delivering therapeutic agents, or substrates to enhance cell growth, differentiation, and migration. Although hydrogels can be prepared from a variety of synthetic polymers as well as biopolymers, the latter are preferred for their inherent biocompatibility. Specifically, keratins are fibrous proteins that have been recently explored for constructing hydrogels useful for RM purposes. The present review discusses the suitability of keratin-based biomaterials in RM, with a particular focus on human hair keratin hydrogels and their use in various RM applications.