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These play an important role for increasing tear stability, wound healing, and anti-
bacterial effects (Mishima 1965 ; Chen et al. 2014 ; Goto et al. 2011 ). To substitute
physiological function of tear proteins, many therapies including albumin eye drops
and autologous serum eye drops have been attempted in current clinical therapies
for severe lacrimal gland dysfunction (Shimmura et al. 2003 ; Kojima et al. 2008 ).
Tears from the bioengineered lacrimal glands have a biological merit because they
contained major tear proteins, such as lactoferrin. The bioengineered harderian
glands could secrete tear lipids to ocular surface. Our results demonstrated that
transplanted bioengineered glands can replace appropriate tear components.
8.6.3 Protection Effect of Ocular Surface by the Bioengineered
Lacrimal Gland
The goal of bioengineered lacrimal gland organ replacement is to protect the ocular
surface from DED. The impaired area on the ocular surface in DED shows corneal
punctate staining and corneal epithelial changes including thinning and stromal
fibroblast activation, which were observed in a DED mouse model with an extra-
orbital lacrimal gland defect (Kaido et al. 2011 ). Our bioengineered lacrimal glands
could prevent these pathological changes in the ocular surface and maintain a
healthy status equivalent to those of normal mice (Fig. 8.4a,b). Our results indicate
that functional replacements of the bioengineered lacrimal gland would be an attrac-
tive therapeutic strategy for severe DED.
8.7 Future Directions of Lacrimal Gland Regenerative
Medicine
Complete substitution of physiological tear function is one of the goals to achieve
stable ocular surface and overcome DED (Hirayama et al. 2013b). Current biologi-
cal analysis of tears and lacrimal glands elucidated a role of key molecules such as
mucin and improved the quality of artificial tear solution (Hamano 1998 ; Shigemitsu
et al. 2002 ; Corrales et al. 2011 ). On the other hand, technological advances in stem
cell biology, developmental biology, and tissue engineering have provided evidence
to realize lacrimal gland regenerative therapy clinically. Especially in treatment for
severe DED, the restoration of the lacrimal gland function including tissue stem cell
transplantation and lacrimal gland organ regeneration has been expected as a cur-
able therapeutic approach (Tsubota et al. 1996 ; Hirayama et al. 2015 ). Our bioengi-
neered lacrimal glands showed a proof of concept for bioengineered organ
replacement to functionally restore the lacrimal gland. To progress this concept
clinically, it requires evidence of efficacy of bioengineered organ transplantation for
disease-specific environment such as inflammation and immunological disorders
M. Hirayama et al.