[Proof of a Concept for Bioengineered Organ Replacement to Restore Lacrimal Gland Function].

The lacrimal gland has an essential role in maintaining a homeostatic environment for a healthy ocular surface by tear secretion. Dry-eye disease, caused by lacrimal gland dysfunction, is a prevalent eye disease that results in corneal epithelial damage. Regenerative medicine, such as stem cell therapy, is expected to be a promising approach to restore the lacrimal gland function. Recently, a novel strategy has been reported of developing a fully functioning bioengineered organ by engraftment of a bioengineered organ germ generated via 3-dimensional cell manipulation using immature stem cells in vitro. We demonstrated an orthotopic transplantation of the bioengineered lacrimal gland germ into adult mice, in which the extra-orbital lacrimal gland has been removed. This mouse model mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germ and harderian gland germ both developed in vivo; they achieved physiological functionality, including tear secretion in response to nervous stimulation and ocular surface protection. This study provided novel evidence for the successful replacement of a fully functional lacrimal gland via engraftment of a bioengineered germ.