Cytotherapy. 2017 Sep 29. pii: S1465-3249(17)30667-9. doi: 10.1016/j.jcyt.2017.08.008. [Epub ahead of print]

Three-dimensional hydrogel culture conditions promote the differentiation of human induced pluripotent stem cells into hepatocytes.

Luo Y¹, Lou C², Zhang S³, Zhu Z¹, Xing Q², Wang P¹, Liu T¹, Liu H¹, Li C¹, Shi W¹, Du Z¹, Gao Y⁴.

Abstract

BACKGROUND AIMS:

Human induced pluripotent stem cells (hiPSCs) are becoming increasingly popular in research endeavors due to their potential for clinical application; however, such application is challenging due to limitations such as inferior function and low induction efficiency. In this study, we aimed to establish a three-dimensional (3D) culture condition to mimic the environment in which hepatogenesis occurs in vivo to enhance the differentiation of hiPSCs for large-scale culture and high throughput BAL application.

METHODS:

We used hydrogel to create hepatocyte-like cell (HLC) spheroids in a 3D culture condition and analyzed the cell-behavior and differentiation properties of hiPSCs in a synthetic nanofiber scaffold.

RESULTS:

We found that treating cells with Y-27632 promoted the formation of spheroids, and the cells aggregated more rapidly in a 3D culture condition. The ALB secretion, urea production and glycogen synthesis by HLCs in 3D were significantly higher than those grown in a 2-dimensional culture condition. In addition, the metabolic activities of the CYP450 enzymes were also higher in cells differentiated in the 3D culture condition.

CONCLUSIONS:

3D hydrogel culture condition can promote differentiation of hiPSCs into hepatocytes. The 3D culture approach could be applied to the differentiation of hiPSCs into hepatocytes for bioartificial liver.