Organoid Models for Salivary Gland Biology and Regenerative Medicine

Figure 1

Salivary gland organoids can be derived from distinct origins by modulating niche factors during in vitro culture. (a) Salivary gland organoids derived from ESCs by a step-wise method that recapitulates the signaling pathways during salivary gland development. ESCs are first inducted towards oral ectoderm fate by exposure to BMP4, TGFβ-i, BMP-i, and FGF2. These oral ectoderm aggregates with the forced expression of Sox9 and Foxc1 develop into branching structures following induction of FGF7 and FGF10. (b) Salivary gland organoids can also be generated from adult stem cells isolated from biopsies. Dissociated cells can be placed in ECM with cytokines important for organogenesis, regeneration, and development including FGF, Wnt3a, R-spondin 1, and TGFβ-i. ESCs: embryonic stem cells; BMP4: bone morphogenetic protein 4; TGFβ-i: transforming growth factor beta inhibitor; BMP-i: bone morphogenetic protein inhibitor; FGF: fibroblast growth factor; ECM: extracellular matrix; Sox9: sex-determining region Y (SRY) box 9; Foxc1: forkhead box C1; Wnt3a: wingless-type MMTV integration site family member 3a; R-spondin1: roof plate-specific spondin 1.