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Cancer stem cells (CSCs) are self-renewing and constitute the primary cause of cancer relapse post-cancer therapy. The CSC niche is composed of various nonmalignant stromal cells that support CSCs' survival during cancer chemoradiotherapy. Understanding the cross-talk between CSCs and stromal cells could pave the way for developing therapeutic strategies to eradicate CSCs. Traditionally, CSC research has been relying on animal models, which can give rise to complications and poor translation in clinical practice. An efficient model to co-culture CSCs and stromal cells is urgently needed. Hence, we leveraged our expertise in enriching CSCs from in vitro cell lines with a 3D alginate-based platform, as reported previously. We established a 3D co-culture system that allowed us to study the interactions between stromal cells and CSCs over an extended period. We showed that the self-renewal capacity and stemness of CSCs were significantly enhanced when co-cultured with 3D cultured human umbilical vein endothelial cells (HUVECs) or a human monocyte cell line (THP1). Strikingly, the expression of MDR1 in 3D co-cultured CSCs was upregulated, leading to enhanced chemotoxic drug tolerance. We suggest that our in vitro co-culture model can impact CSC research and clinical practice when the goal is to develop therapeutics that target and eradicate CSCs by targeting stromal cells.

Rotary cell culture systems (RCCS) have been shown to be promising for promoting three-dimensional (3D) cell growth and assembly of cells into functional tissues. In this study, 3D tissue-like spheroids of MCF-7 cells were constructed by encapsulating the cells in the collagen-alginate hydrogel, and then cultured in a RCCS to investigate the proliferation of MCF-7 cells. The results from the MTT assay showed that the proliferation rate of MCF-7 cells cultured in the RCCS was higher than that of the static culture control group, and the results from the flow cytometry revealed that the cells in S and G2/M phase were significantly increased compared to the control group. The expression of cell proliferation antigen PCNA and cyclin D1 was also examined with the results further supporting the enhanced proliferation of MCF-7 cells by the RCCS. The results from indirect immunofluorescence revealed that the rotary culture altered neither the cytoskeleton distribution nor the assembly of mitotic spindle. By examination, it was also shown that the rotary culture induced the ERK1/2-MAPK pathway. Taken together, this study demonstrated that the rotary culture could promote the proliferation of MCF-7 cells by inducing the ERK1/2 pathway.

The immune‐mediated foreign body response to biomaterial implants can trigger the formation of insulating fibrotic capsules that can compromise implant function. To address this challenge, the intrinsic bioactivity of the mucin biopolymer, a heavily glycosylated protein that forms the protective mucus gel covering mucosal epithelia, is leveraged. By using a bioorthogonal inverse electron demand Diels–Alder reaction, mucins are crosslinked into implantable hydrogels. It is shown that mucin hydrogels (Muc‐gels) modulate the immune response driving biomaterial‐induced fibrosis. Muc‐gels do not elicit fibrosis 21 days after implantation in the peritoneal cavity of C57Bl/6 mice, whereas medical‐grade alginate hydrogels are covered by fibrous tissues. Further, Muc‐gels dampen the recruitment of innate and adaptive immune cells to the gel and trigger a pattern of very mild activation marked by a noticeably low expression of the fibrosis‐stimulating transforming growth factor beta 1 cytokine. Macrophages recruited to Muc‐gels upregulate the gene expression of the protein inhibitor of activated STAT 1 (PIAS1) and SH2‐containing phosphatase 1 (SHP‐1) cytokine regulatory proteins, which likely contributes to their low cytokine expression profiles. With this advance in mucin materials, an essential tool is provided to better understand mucin bioactivities and to initiate the development of new mucin‐based and mucin‐inspired "immune‐informed" materials for implantable devices subject to fibrotic encapsulation. [ABSTRACT FROM AUTHOR]