AATEX Special issue on "Application of 3D culture for human cells as an alternatives to animal experiments"

Abstract

In the opening lecture of the 26^th Annual Meeting of JSAAE in 2013 (Imai, 2013), Prof. K. Imai stated that three-dimensional (3D) culture was first introduced in 1952 by Prof. A. Moscona, using the "watch-glass method" or "hanging drop culture" (Moscona and Moscona, 1952) and was further advanced by Prof. Y. Kuroda, using "aggregation culture" in 1963 (Kuroda, 1963). Prof. Y. Kuroda received an award from the Japanese Society for Alternatives to Animal Experiments in 2004 for his studies. In 1986, Prof. N. Takahashi reported a technique for the isolation and long-term culture of rat hepatocytes by 3D culture (Takahashi, 1986). Subsequently, Prof. N. Koide reported the "spheroid culture" technique for primary rat hepatocytes (Koide et al., 1990).

When we reported our study on 3D culture in 1991 (Matsushita et al., 1991), the total number of papers retrieved in PubMed, using "three dimensional culture" as the key words, was only 85 per year (Fig. 1). In 2015, the number of papers retrieved per year increased to 927 and on December 17, 2016, the total cumulative number reached 10729, as shown in Fig. 1. When the key word "cancer" was added to the search, the number of papers retrieved was 2337, and when the key word "primary" was added to the search, the number became 1314. Additionally, when "screening" or "toxicity" was added to the search, the number of papers retrieved was 838 or 397, respectively. Furthermore, when the key word "human" was added to the search, the number of papers retrieved was 6313 (Ishii et al., 2015; Ishii et al., 2016). These retrieval results suggest that the 3D culture of human cancer cells appears to be applied to drug screening, and the 3D culture of human primary cells appears to be applied to toxicity test and metabolite analysis of chemical compounds, including drug candidates.

In this special issue on the "Application of 3D culture for human cells as alternatives to animal testing and experimentation," T. Iwasa et al. report a 3D culture of rat hepatocytes, using a new 3D culture scaffold called "Cellbed" for liver toxicity testing. Y. Kuroda et al. reported a suspended aggregation culture of cryopreserved human hepatocytes and hepatoma cell line, HepG2, using a newly developed low-acyl gellan gum, FP001, and T. Kubo et al. reported a 3D culture of a hepatic progenitor cell line, HepaRG, using VECELL Inserts, which consist of type I collagen-coated expanded polytetrafluoroethylene (ePTFE) mesh. These studies describe the new 3D culture technologies for hepatocytes or hepatic progenitor cells and include promising and informative results for the application of 3D culture for toxicity tests and metabolite analysis of chemical compounds as alternatives to animal testing and experimentation in the near future.