145(Tiwari et al. 2012 ). Another demand for regenerating the lacrimal gland would be
the use of available cell sources including pluripotent stem cells (Yoshida and
Yamanaka 2011 ; Okano and Yamanaka 2014 ; Tsumaki et al. 2015 ). Application to
3D organ regeneration using embryonic stem cells and induced pluripotent stem
cells to regenerate lacrimal glands would be powerful tools not only to realize func-
tional lacrimal gland organ replacement but also to investigate developmental and
pathological process of the lacrimal gland function (Okano 2010 , 2012 ; Okano and
Yamanaka 2014 ). Bioengineered organ regeneration is expected to be the next-
generation therapeutic strategy of regenerative medicine.
Acknowledgments This work was partially supported by a Grant-in-Aid for Scientific Research
A (to T.T.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Conflicts of Interest The authors declare no conflict of interest.
aBioengineeredDefectNormalFluorescein
image Impaired areabBioengineeredDefectNormalCorneal epitheliumFig. 8.4 Tear secretion and ocular surface protection for the bioengineered lacrimal gland.
Representative images of the corneal surface of a normal lacrimal gland (upper), a lacrimal gland-
defective mouse (center), and a bioengineered lacrimal gland-engrafted mouse (lower). The punc-
tate staining area by fluorescein showed impaired area on the corneal surface. Scale bar, 1 mm
(Modified and reprinted from Hirayama et al.^112 )
Representative microscopic images of the corneal epithelium including a normal mouse (upper),
lacrimal gland-defective mouse (center), and bioengineered lacrimal gland-transplanted mouse
(lower) are shown. Chronic dry eye status in lacrimal gland-defective mouse induced corneal
thickening as shown in the center panel, whereas these changes were not observed in the bioengi-
neered lacrimal gland-transplanted mouse. Scale bars, 25 μm. (Modified and reprinted from
Hirayama et al^112 )
8 Functional Lacrimal Gland Regeneration