In vitro constructing a of three-dimensional hepatocarcinoma model for drug screening / 中国组织工程研究

ABSTRACT

BACKGROUND:In vitro construction of three-dimensional (3D) tumor model has been growing to substitute two-dimensional (2D) tumor model for drug screening. OBJECTIVE:To develop 3D hepatocarcinoma model for the sensitive study of antitumor drugs. METHODS:Taking HepG2 as cellmodel, hydrogel scaffold was fabricated with chitosan/col agen to construct in vitro 3D hepatocarcinoma model. The 3D hepatocarcinoma aggregates were characterized regarding to the morphology, growth and cytoskeleton distribution and so on. Final y, the sensitive assay of in vitro 3D hepatocarcinoma model to the clinical antitumor drugs was studied with 2D hepatocarcinoma model as control. RESULTS AND CONCLUSION:(1) HepG2 cells in chitosan/col agen scaffold grew to form 3D cellaggregates after 10-day culture. (2) Although the growth rate of HepG2 cells in chitosan/col agen scaffold was slightly slower than that of cells in 2D culture, the HepG2 cellviability of 3D culture could be maintained longer. (3) It was found that the fibrin skeleton of HepG2 cells in chitosan/col agen scaffold rearranged and displayed structural similarity to in vivo hepatic tissue. (4) The sensitivity of in vitro 3D hepatocarcinoma model to the clinical antitumor drugs was significantly lower than that of 2D cells. In conclusion, the in vitro 3D hepatocarcinoma model developed in chitosan/col agen scaffold provided cytoskeleton structure closer to in vivo hepatic tissue, which is potential system for in vitro drug screening.