Matrigel, they developed into functional ductal/acinar structures. Thus, stem cells isolated either from embryos or from adult tissues could give rise to organoids. In 2009, Sato et al. (2009) used stem cells that express Leu-rich repeat–containing G protein–coupled receptor 5 isolated from primary intestinal tissue and showed that these stem cells could clonally generate crypt–villus architecture in 3D culture. Based on the mammary gland literature, these authors also used Matrigel to carry out their 3D cultures and supplemented them with factors required for the growth of intestinal epithelium. Crypt organoids were generated, consisting of a central lumen lined by villus-like epithelium and several surrounding crypt-like domains (Sato et al., 2009). This methodology was then successfully used in cultures of stomach (Barker et al., 2010), pancreas (Huch et al., 2013a), colon (Sato et al., 2011), and liver (Huch et al., 2013b). Mouse and human embryonic stem cells have also been used to generate organoids in a dish, such as polarized cortical brain tissues (Eiraku et al., 2008) and optic cups (Eiraku et al., 2011; Nakano et al., 2012). Induced pluripotent stem cells, a breakthrough that took place in 2007, have provided an additional tool to study morphogenesis (Takahashi et al., 2007;
