WWW.WAS.ORG • WORLD AQUACULTURE • SEPTEMBER 2023 59 (CONTINUED ON PAGE 60) Cancer Research: Fathead minnow cells and goldfish fibroblast cell lines are used to study mechanisms and causes of cancer and also to identify effective drugs to selectively destroy cancer cells (Hightower and Renfro 1988). Rainbow trout cell lines were used for investigating the carcinogenic effects of aflatoxin B (Bailey et al. 1982). Research on Fish Parasites: Several FCLs have been used to study the development and pathogenesis of fish parasites including Ichthyophthirius multifiliis, Glugea plecoglossi, salmonid microsporidian parasite, Gyrodactylus sp., and Loma salmonae (Kim et al. 1999, Nielsen and Buchmann 2000, Shaw et al. 2001). Kou et al. (1995) developed a cell line from the tissues of Japanese eel elvers (Anguilla japonica) infected with Pleistophora anguillarum. Regenerative Therapy: Reconstitution of skin following severe burns is considered the most successful application of cell-based regenerative therapy. In this regard, FCLs are experimentally utilized for producing artificial skin to treat patients with burns and ulcers. Three-dimensional Cell Lines: Compared to the traditional 2-D cultures, 3-D cell cultures are apt models to study complex physiological processes in vitro as cells interact with their surroundings in all three dimensions. The 3-D cell line spheroids developed from rainbow trout successfully propagated Saprolegnia parasitica spores (Faber et al. 2021). FCLs combined with 3-D culture platforms will be relevant models for drug screening and biomedical research. Genetic Research: Since cell culture environments can be easily manipulated, new genes can be delivered into the cells for genetic studies. Dehler et al. (2016) carried out the first gene editing in an FCL. Several successful gene editing trials in FCLs were reported afterwards to study fish diseases, antimicrobial resistance and other processes (Ma et al. 2018, Wang et al. 2018, Collet et al. 2018, Gratacap et al. 2020). et al. 1982, Bermejo-Nogales et al. 2017, Leme 2019) with the benefit of avoiding high costs and variability of results. Additionally, FCLs are used to evaluate bacterial and fungal toxins (McIntosh et al. 1997, Ku et al. 2009). FCL-Based Production of Biologicals: Cell lines allow for the large-scale production of commercially relevant biologicals including vaccines, hormones, antibodies, enzymes, and growth factors (Lovitt et al. 2014, Maguire 2016, Verma et al. 2020). Numerous FDAapproved therapeutic proteins are generated using human cell lines and other mammalian cell cultures (Dumont et al. 2016). Comparatively, FCLs are less expensive and therefore more economical for the mass production of biologicals. Drug Screening and Development: Cell linebased assays have become an inevitable part of the pharmaceutical industry for high throughput screening of potential compounds and to test the cytotoxicity of candidate drugs. Other related applications include dose optimization, drug delivery, drug safety, pharmacology, cellular targeting, pharmaceutical analysis, and quality assurance (Villena 2003, Allen et al. 2005). The first phase of drug administration is done using cell lines to test the efficiency and dosage, then on to animals and finally to humans. Fish cell cultures can potentially play an important role in the research and development of drugs aimed to benefit fish. Stem Cell Research: Stem cells can differentiate into different cell types and are used in embryological, genetic, and biotechnology studies. Embryonic cell lines have been established from catfish, Nile tilapia and several marine fish species (Chen et al. 2007, Fan et al. 2017, Vergès-Castillo et al. 2021). Embryonic germ cell transplantation was successfully used for surrogate production in salmonids (Yoshizaki et al. 2010). From the testis of medaka fish, Hong et al. (2004) developed a spermatogonial cell line which produced viable sperm. With hybrid catfish (♀ channel catfish x ♂ blue catfish) production, blue catfish are sacrificed for sperm collection. Development of a blue catfish spermatogonial cell line could be of potential benefit to the industry. FIGURE 3. Susceptibility of catfish cell line to viruses. (b, c) Cells inoculated with catfish viruses exhibited CPEs, while no CPEs (d) were observed in cells inoculated with koi herpesvirus (Aarattuthodi et al. 2022). FIGURE 2. Cytopathic effects (CPEs) displayed by viruses. (a) healthy catfish cell line, (b) cells infected with catfish virus displaying CPEs such as rounding of cells, clumping of cells, and destruction of cell monolayer. Other types of CPEs can be vacuoles and cytoplasmic inclusion bodies (Dharan et al. 2021; Aarattuthodi et al. 2022).