Functional lacrimal gland regeneration

The lacrimal gland is an indispensable organ to secrete tear for maintaining a homeostatic microenvironment for healthy ocular surfaces. The lacrimal gland develops from its organ germ at ocular epithelium via epithelial and mesenchymal interactions into mature secretory gland structure, which consists of acini, ducts, myoepithelial cells, and peripheral tissues such as nerves. Dysfunction of the lacrimal gland leads to dry eye disease, which is one of the prevalent eye disorders involving ocular discomfort, significant visual disturbances, and a reduced quality of life. Current clinical therapies for dry eye disease are artificial tear eye drops, but they are transient and palliative approach. To restore functions of the lacrimal gland, lacrimal tissue stem cells have been identified for regenerative therapeutic approaches. Fully functional organ replacement such as for tooth and hair follicles has also been developed as a novel three-dimensional organ regeneration using stem cell manipulation-named the organ germ method. Recently, we successfully demonstrated fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ. This study was a significant advance in possible lacrimal gland organ replacement as a next-generation regenerative therapy for dry eye disease. In this review, we summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy.