Development-inspired approach for the derivation of functional and transplantable salivary gland organoids from human pluripotent stem cells

Salivary gland (SG) hypofunction significantly affects the life quality of patients with hyposalivation. Current treatment options for these conditions are limited and often result in undesirable side effects. To address this issue, we’ve developed a developmentally inspired strategy to derive salivary gland epithelial progenitor (SGEP) cells from human pluripotent stem cells (PSC). Then we employ SGEP cells derived from human PSC with a SOX10::GFP reporter to engineer three-dimensional lumenized SG organoids, with well-defined lumens and secretory function, reminiscent of human salivary glands. Upon transplantation into the submandibular gland of athymic nude mice, mCherry+ salivary gland organoids (SGO) integrate into the gland and differentiated into salivary gland phenotypes, including acinar, ductal and myoepithelial structures. Our findings suggest that SG organoids may hold promise for studying SG development, disease progression and drug screening, as well as for development of cell therapies for salivary gland regeneration. Here, they generate salivary gland epithelial progenitors hPSCs by mimicking in vivo salivary gland development. These progenitors self-assemble into salivary gland organoids in vitro and reconstituted both acinar and ductal structures upon orthotopic transplantation in vivo.