Influence of a three-dimensional, microarray environment on human cell culture in drug screening systems.
نویسندگان
چکیده
We have used a modified 3D cellular microarray platform for the high-throughput analysis of growth, cytotoxicity, and protein expression profile of a human hepatocellular carcinoma cell line, HepG2, in alginate. The results obtained were compared to analogous studies in 2D and 3D environments at the microtiter scale. The antiproliferative effects of four drugs, tamoxifen, 5-fluorouracil, doxorubicin, and amitriptyline, were studied as a function of seeding density in the three different culture platforms. The chemosensitivity of HepG2 cells to all four compounds decreased substantially with increasing cell number in the 2D and 3D microtiter-based cultures, while no seeding density dependence was observed in the IC(50) values obtained in the 3D microarray culture platform. These results can be rationalized based on the development of confluence-dependent resistance in cultures where proliferation is restricted by cell-cell contacts and nutrient availability, as is the case for both of the microtiter-based cultures. Additionally, further development of an on-chip, in-cell immunofluorescence assay provided quantitative data on the levels of specific target proteins involved in proliferation, adhesion, angiogenesis and drug metabolism, and was used to compare expression profiles between 2D and 3D environments. The up-regulation of several CYP450 enzymes, β1-integrin and vascular endothelial growth factor (VEGF) in the 3D microarray cultures suggests that this platform provides a more in vivo-like environment allowing cells to approach their natural phenotype.
منابع مشابه
A Quick update from the Past to Current Status of Human Pluripotent Stem Cell-derived Hepatocyte culture systems
Pluripotent stem cells (PSCs) may be offered as an unlimited cell source for the hepatocyte generation. The generation of hepatocytes from stem cells in vitro would provide an alternative cell source for applications in drug discovery and cell transplantation. In this review, we discuss different approaches to generate pluripotent stem cell-derived hepatocytes, advantages, limitations for each ...
متن کاملEvaluation of Human Breast Adenocarcinoma (MCF-7) Cells Proliferation in Co-Culture with Human Adipocytes in Three Dimensional Collagen Gel Matrix: Norepinephrine as a Lipolytic Factor
Background: Norepinephrine plays a trophic role in the control of cell replication and differentiation in target cells that express adrenergic receptors. Methods: In this study, we have tested the influence of infraphysiological, physiological and supraphysiological concentrations (0.0001 nM, 1 nM, 10000 nM) of human norepinephrine on the proliferation of breast cancer cells (human breast adeno...
متن کامل***Removed from the Issue*** Application of Cell-Based Assay Systems for the Early Screening of Human Drug Hepatotoxicity in the Discovery Phase of Drug Development
متن کامل
ذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Biomaterials
دوره 33 35 شماره
صفحات -
تاریخ انتشار 2012