Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

Abstract

A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC), express markers similar to mammary stem cells, and are highly resistant to chemotherapy. Currently, study of BCSC is hampered by the inability to propagate these cells in tissue culture without inducing differentiation. Recently, it was reported that proliferation and differentiation can be modified by culturing cells on electrospun nanofibers. Here, we sought to characterize the chemoresistance and stem-like properties of breast cancer cell lines grown on nanofiber scaffolds. Cells cultured on three-dimensional templates of electrospun poly( ε -caprolactone)-chitosan nanofibers showed increases in mammary stem cell markers and in sphere-forming ability compared with cells cultured on polystyrene culture dishes. There was no increase in proliferation of stem cell populations, indicating that culture on nanofibers may inhibit differentiation of BCSC. The increase in stemness was accompanied by increases in resistance to docetaxel and doxorubicin. These data indicate that BCSC populations are enriched in cells cultured on electrospun poly( ε -caprolactone)-chitosan nanofibers, scaffolds that may provide a useful system to study BCSC and their response to anticancer drug treatment.

Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells

“…Chitosan modified with other molecules has been recently used as culture systems for the investigation of tumor progressions and has been shown to increase the cancer stemness23242526. In the current study, we considered that the pristine chitosan per se could promote the properties of CSCs including migration ability, drug resistance, quiescent population, and self-renewal capacity through in colon cancers.…”

“…Chitosan crosslinked with other molecules has also been used to culture cancer cells2324. For instance, porous chitosan-alginate scaffolds may enrich the CD133 + glioblastoma CSC population25 and electrospun polycaprolactone-chitosan scaffolds may increase the breast cancer stemness26. However, the mechanisms of interactions between cells and biomaterials are still unknown.…”

TiO2/PCL hybrid materials synthesized via sol–gel technique for biomedical applications

“…The positive effect of PCL was in accordance with the wide use of this synthetic hydrophobic polymer in biomedical and drug delivery devices. In fact, it is broadly demonstrated that its slow degradation kinetics, biocompatibility, and semicrystalline nanofibers are able to simulate the extracellular matrix providing a good scaffold for cell growth and engineering [39,40]. Data from Trypan Blue dye exclusion assays also highlighted that the number of Trypan Blue positive dead cells after the addition of the hybrid materials decreased significantly in a PCL-dose dependent way (Fig.…”

Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling

“…[129] Similarly, using composite electrospun PCL/chitosan nanofiber scaffolds to culture MCF-7 and T47-D breast cancer cells led to enrichment of CD44 − /CD24 − cells highly capable of forming mammospheres. [130] These cells isolated from the scaffold and cultured in microplates showed greater resistance to treatment with docetaxel and doxorubicin. Although mechanisms of enrichment of breast cancer stem cells was not fully explored, the technique enabled enrichment of cancer stem cells for drug discovery against these inherently drug-resistant cells.…”