12/27/2023 0 Comments Foster freeze carson![]() ![]() Recently, various three-dimensional (3D) cell culture systems have been developed as alternative in vitro platforms for improved understanding of cancer biology. Moreover, testing therapeutic agents in animal xenografts is expensive, tedious and time consuming, thus further delaying the translation of new technologies from bench to bedside. Although studies based on animal models predict more pathologically relevant outcomes, the presence of many uncontrollable variables associated with these models makes it challenging to determine the impact of specific factors on tumor progression or to identify the therapeutic efficacies of novel personalized medicine. Because of the lack of spatial guidance cues needed to establish proper cell-cell contacts and cell-matrix interactions, 2D cell cultures are physiologically irrelevant and experimentally unreliable. ![]() However, both monolayer cultures and xenografts have inherent limitations. ![]() Using these complementary systems, researchers have gained improved understanding of cancer biology and have developed many efficacious anti-cancer treatment methods. Overall, the HA model system provides a useful platform for the study of tumor cell responses to growth factors and for screening of anticancer drugs targeting these pathways.įor decades, cancer biologists relied on two-dimensional (2D) monolayer cell culture platforms and/or in vivo animal models (xenografts) to investigate the complex mechanisms of tumorigenesis, angiogenesis, invasion and metastasis. Compared to cells cultured on 2D, the engineered tumoroids significantly increased the expression of two pro-angiogenic factors, vascular endothelial growth factor-165 (VEGF 165) and interleukin-8 (IL-8), both at mRNA and protein levels. Cells in 3D hydrogels assemble into spherical tumoroids, form close cellular contacts through E-cadherin, and show cortical organization of F-actin, whereas those plated as 2D monolayers adopt a spread-out morphology. LNCaP cells embedded in the bottom layer receive the growth factor signals from the top, and in response form enlarging tumoroids with an average diameter of 85 μm by day 7. ![]() In our bilayer hydrogel construct, the top layer contains heparin (HP)-decorated, HA-based hydrogel particles (HGPs) capable of releasing heparin-binding epidermal growth factor-like growth factor (HB-EGF) in a sustained manner at a rate of 2.5wt%/day cumulatively. The orthogonal and cytocompatible nature of the crosslinking chemistry permits facile incorporation of cytokine-releasing particles and PCa cells. The resultant viscoelastic gels have an average elastic modulus of 234 ± 30 Pa and can be degraded readily by hyaluronidase. HA hydrogels were prepared by mixing solutions of HA precursors functionalized with acrylate groups (HA-AC) and reactive thiols (HA-SH) under physiological conditions. In this study, a hyaluronic acid (HA)-based bilayer hydrogel system that not only supports the tumoroid formation from LNCaP prostate cancer (PCa) cells, but also simulates their reciprocal interactions with the tumor-associated stroma was developed and characterized. Cancer cells cultured in physiologically relevant, three-dimensional (3D) matrices can recapture many essential features of native tumor tissues. ![]()
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