Epithalial cells for spheroid formation
The Epithelium is a thin, continuous, layer of tightly packed cells formed as complex 3D structures such as cysts, tubules or invaginations. The shape of the epithelium is essential for its function as it aids in creating biochemical gradients that directs cell placement and compartmentalization. In addition to providing protection to underlying tissues, all epithelial cells perform a wide array of vital functions such as diffusion, filtration, secretion, trans cellular transport etc. that is crucial for proper organ function. The adult stem cells present within epithelial tissues ensure rapid repair and regeneration of cells (Crosnier et al, 2006, Torras et al, 2018, Vrana et al, 2013) .
Epithelial cell models used in Patho-physiological research
There is a wide range of systems currently utilized for basic function studies, disease modeling, drug discovery, and tissue regeneration studies; albeit some being more effective than others. There are conventional animal models that are used to study basic, in-vivo physiology and tissue interactions, but are unable to provide translatable information on human response due to species differences. 2D cell culture models are able to simulate early cellular response, but have poor predictive capabilities (Griffith et al, 2006). 3D culture technology has helped to overcome these limitations, as it provides native state structures on a reliable, reproducible in-vitro system. There are many application-specific 3D models of epithelial tissues, ranging from self-assembled cultures (i.e. spheroids or organoids), lab on chip devices, and engineered micro tissues (Torras et al, 2018).
Self-assembled 3D cultures
Spheroids and organoids have gained recognition as a reliable in-vitro tool used routinely for drug testing and disease modeling. Organoids are a excellent system for basic science research, as well as patient-specific disease modeling, as it provides a comprehensive complex 3D cell culture with a native-state like cell composition, structure and function. Spheroids are commonly used in cancer research as the spherical structure recapitulates effectively the biochemical and cellular environment present in most tumors (Lin et al, 2008). To this end, tumor specific epithelial cells are produced from primary cancer cells from gliomas, breast, colon, ovary and prostate tumors (Ishiguro et al, 2017).
Breast cancer lines such as D492HER, D492, MCF10A, MDA-MB231, MCF-7, HCC143 as well as epidermoid carcinoma cell lines (A431) can be easily cultured as spheroids to yield a reliable and adaptable system for pharmacological studies (https://facellitate.com/wp-content/uploads/FAQs_new-2.pdf) . In addition to being relatively simple to perform, and cost effective, spheroid cultures are also highly reproducible and modifiable making it an attractive method for high throughput drug screens.
- Vrana, N. E., Lavalle, P., Dokmeci, M. R., Dehghani, F., Ghaemmaghami, A. M., and Khademhosseini, A. (2013). Engineering functional epithelium for regenerative medicine and in vitroorgan models: a review. Tissue Eng. Part B Rev. 19, 529–543. doi: 10.1089/ten.teb.2012.0603
- Crosnier, C., Stamataki, D., and Lewis, J. (2006). Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Rev. Genet.7, 349–359. doi: 10.1038/nrg1840
- Lin, R. Z., and Chang, H. Y. (2008). Recent advances in three-dimensional multicellular spheroid culture for biomedical research. J.3, 1172–1184. doi: 10.1002/biot.200700228
- Ishiguro, T., Ohata, H., Sato, A., Yamawaki, K., Enomoto, T., and Okamoto, K. (2017). Tumor-derived spheroids: relevance to cancer stem cells and clinical applications. Cancer Sci.108, 283–289. doi: 10.1111/cas.13155
- Griffith, L. G., and Swartz, M. A. (2006). Capturing complex 3D tissue physiology in vitro. Rev. Mol. Cell Biol.7, 211–224. doi: 10.1038/nrm1858