Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

Abstract

The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.

Feasibility Assessment of Polyvinyl Alcohol-Based Bioresorbable Cardiovascular Stents Manufactured via Solvent-Cast Direct Writing Extrusion

“…-Following the laboratory sterilization protocol previously reported in other studies, samples were subjected to overnight sterilization in ethanol, followed by an additional 30 minutes of ultraviolet exposure [20]. The test specimens were sterilized by immersing the material in absolute ethanol (Panreact, Spain) for 24h.…”

The solvent chosen for the manufacturing of electrospun polycaprolactone scaffolds influences cell behavior of lung cancer cells

“…Nanofibers manufactured using electrospinning technique exhibit a filament size similar to ECM and a high surface area-to-volume ratio allowing cell attachment 10 . Polycaprolactone (PCL) is usually chosen to manufacture electrospun scaffolds, which have been proved to be a useful 3D cell culture for lung cancer stem cell population 11 . This synthetic polymer is suitable for biomedical engineering and cell culture applications because its low melting temperature, biocompatibility, long-term biodegradability, bioresorbability, and inexpensive price 12 , 13 .…”