Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

Masatoshi Hirayama,Masamitsu Oshima,Kazutaka Ikeda,Kazuo Tsubota,Miho Ogawa,Yurie Sekine,Kentaro Ishida,Shigeto Shimmura,Kentaro Yamashita,Tetsuya Kawakita,Takashi Tsuji

doi:10.1038/ncomms3497

Masatoshi Hirayama, Masamitsu Oshima + Show 9 more

Open Access

https://doi.org/10.1038/ncomms3497

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Abstract

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. Dry-eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye diseases that cause corneal epithelial damage and results in significant loss of vision and a reduction in the quality of life. Here we demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. This study demonstrates the potential for bioengineered organ replacement to functionally restore the lacrimal gland.

Highlights

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion
Lacrimal glands, which consist of a main gland and small accessory glands, have a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface through tear secretion[1]
Dry-eye disease (DED), which is caused by tear shortage, results from lacrimal gland dysfunction caused by systemic diseases and environmental exposures, such as Sjogren’s syndrome and ocular cicatricial pemphigoid, or from other causes, including aging, long-term work with a visual display, dry room environments, the use of contact lenses and refractive surgery[8,9,10]

Summary

Introduction

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. We demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. The tear film is a trilaminar fluid composed of a superficial lipid layer, an intermediate aqueous layer and an underlying mucous layer This film covers the entire ocular surface, including the bulbar and palpebral conjunctiva, and the cornea[3]. The bioengineered lacrimal and harderian gland germs, both developed in vivo, achieved sufficient physiological functions, including tear production in response to pilocarpine and menthol stimulation and ocular-surface protection. Our current study provides the potential for bioengineered lacrimal gland replacement to restore lacrimal gland function

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Results

Conclusion