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.
Gene editing is a process by which single base mutations can be corrected, in the context
of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs). The survival and
proliferation of the corrected cells bearing modified genes, however, are impeded by a
phenomenon known as reduced proliferation phenotype (RPP); this is a barrier to practical
implementation. To overcome the RPP problem, we utilized nanofiber scaffolds as templates
on which modified cells were allowed to recover, grow, and expand after gene editing.
Here, we present evidence that some HCT116-19, bearing an integrated, mutated enhanced
green fluorescent protein (eGFP) gene and corrected by gene editing, proliferate on
polylysine or fibronectin-coated polycaprolactone (PCL) nanofiber scaffolds. In contrast,
no cells from the same reaction protocol plated on both regular dish surfaces and
polylysine (or fibronectin)-coated dish surfaces proliferate. Therefore, growing
genetically modified (edited) cells on electrospun nanofiber scaffolds promotes the
reversal of the RPP and increases the potential of gene editing as an ex vivo
gene therapy application.
Polycaprolactone (PCL) and its blended composites (chitosan, gelatin, and lecithin) are well-established biomaterials that can enrich cell growth and enable tissue engineering. However, their application in the recovery and proliferation of genetically modified cells has not been studied. In the study reported here, we fabricated PCL-biomaterial blended fiber membranes, characterized them using physicochemical techniques, and used them as templates for the growth of genetically modified HCT116-19 colon cancer cells. Our data show that the blended polymers are highly miscible and form homogenous electrospun fiber membranes of uniform texture. The aligned PCL nanofibers support robust cell growth, yielding a 2.5-fold higher proliferation rate than cells plated on standard plastic plate surfaces. PCL-lecithin fiber membranes yielded a 2.7-fold higher rate of proliferation, while PCL-chitosan supported a more modest growth rate (1.5-fold higher). Surprisingly, PCL-gelatin did not enhance cell proliferation when compared to the rate of cell growth on plastic surfaces.
This article suggests that although crime and deviance are subject to the dynamics of global socio-economic-political events, the field of criminology can have a marked, positive impact in this realm. To achieve this end, there is a need to advance interdisciplinary criminology and/or criminal justice education worldwide, to embrace systematic, evidence-based program and policy evaluation, and to become effective political and scientific criminologists. Criminology is not a mature science at this point, and we are not certain how to systematically respond to the crime problem. We lack accurate diagnostic instruments, a definitive body of knowledge, and an understanding of cause and effect, and we do not possess a series of generally consistent treatment modalities. In this context, criminologists are somewhat akin to physicians of the 18th century.
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