Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

TLDR

Salivary gland hypofunction, or xerostomia, arises from radiation therapy, Sjögren's syndrome, or aging and leads to dental decay, infection, mastication and swallowing dysfunction, and reduced quality of life. The study demonstrates full functional regeneration of a salivary gland by orthotopic transplantation of a bioengineered germ that reproduces morphogenesis via reciprocal epithelial–mesenchymal interactions. The engineered germ matures into a gland with acinar structures, myoepithelium, and innervation. The regenerated gland produced saliva in response to pilocarpine and gustatory stimulation, protected against oral bacterial infection, restored normal swallowing in a salivary gland‑defective mouse model, and demonstrates proof‑of‑concept for treating xerostomia.

Abstract

Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren's syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia.