Human iPSC-derived salivary gland cell sheets integrate with injured glands to form glandular structures.

Functional integration of transplanted cells with host tissue remains a major challenge in cell-based therapies for tissue damage in organs with complex structures, such as exocrine glands. In this study, we investigated whether salivary gland organoids derived from human induced pluripotent stem cells (hiPSCs) could be integrated into injured salivary glands using cell sheet engineering. Cell sheet engineering has demonstrated therapeutic potential in a range of organs, including the heart, retina, and lungs. We found that hiPSC-derived salivary gland organoids contain long-term maintainable progenitor cells, and the resulting cell sheets exhibited heterogeneity, including acinar, ductal, and myoepithelial cells. Furthermore, transplantation of the organoid-derived salivary gland cell sheets into immunodeficient mice resulted in partial integration with the host salivary ducts, leading to the formation of structures that included xenogeneic chimeric ducts. These findings suggest that salivary gland cell sheet transplantation represents a promising strategy for functional salivary gland regeneration.