Anti-Cancer Drug Screening Based on a Adipose-Derived Stem Cell/Hepatocyte 3D Printing Technique

Abstract

Background: During the last several decades, drug screening results based on two-dimensional (2D) cell cultures could hardly be duplicated by animal experiments due to different cell growth environments. With the development of three-dimensional printing (3DP) techniques, in vitro 3D cell cultures show great advantages in many areas. In this study, a 3D drug screening model based on a cell-laden gelatin/alginate/fibrinogen hydrogel was established using a cell 3D printer developed in Tsinghua University.Methods: 2D and 3D drug screening effects were compared with three anti-liver tumor drugs (i.e. astragalus polysaccharide, 5-Fluorouracil and matrine). Cell survival rates were tested using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyl tetra-sodium bromide colorimetric and cell counting kit-8 methods. Some other detection methods, such as 4',6-diamidino-2-phenylindole/5- or 6-(N-Succinimidyloxycarbonyl)-3',6'-O,O'-diacetylfluorescein staining, acridine orange/propidium iodide staining, hematoxylin-eosin staining and scanning electron microscope, were applied to assist the analyses.Results: Cell viability of the 3D adipose-derived stem cell/hepatocyte cocultures was increased. The 3D model enhanced the drug-resistance of hepatocytes.Conclusion: This in vitro 3D model has promise to be widely used in drug screening.