141been trialed in human (Sant’ Anna et al. 2012 ; Marinho et al. 2010 ). The results
seem promising preliminary; however, a more extensive study under well-
constructed clinical research for long term is expected (Sant’ Anna et al. 2012 ).
Recent advances in regenerative medicine and stem cell biology have shown another
possibility in regenerating a functional lacrimal gland.
8.5 Investigation of Lacrimal Gland Stem/Progenitor Cells
in Adult Tissue
Self-renew response after partial tissue injury by activation of tissue stem cells has
been observed in secretory glands, including the salivary glands, pancreas, and
mammary glands (Takahashi et al. 1998 ; Feng et al. 2009 ; Sumita et al. 2011 ;
Lanzoni et al. 2015 ; Linnemann et al. 2015 ). A concept of cell injection therapy
using purified tissue stem cells came to be considered as an established method to
restore damaged tissue (Copelan 2006 ; Segers and Lee 2008 ). In the lacrimal glands,
many researchers have tackled to elucidate existence and details of tissue stem cells.
An induced partial damage of mouse lacrimal gland’s tissue using cytokine such as
IL-1 leads to inflammation and cell death; however, some processes of tissue repair
occur (Zoukhri et al. 2007 ). In the damaged lacrimal glands, increase of nestin-
positive mesenchymal cells and cells expressing stem cell markers such as ABGC2
and Sca-1 has been reported (You et al. 2011 , 2012 ; Zoukhri 2010 ). Activation of
mesenchymal stem cells and epithelial-mesenchymal transition is thought to involve
this regenerative capacity of the lacrimal glands (You et al. 2012 ). In in vitro culture
of human lacrimal gland cells, candidates of tissue stem cell expressing stem cell
markers such as c-Kit, ABCG2, and ALDH1 have been determined (Tiwari et al.
2012 ). Tissue regeneration by tissue stem cell injection in adult tissues to recover
lacrimal gland function is a critical subject of intense research because of the poten-
tial clinical benefits.
8.6 Functional Lacrimal Gland Organ Regeneration
by Transplantation of a Bioengineered Organ Germ
Functional design of organs is built up through an embryonic developmental pro-
cess in coordination with kinetics and interactions of various types of cells. Organ
replacement regenerative therapy using a fully functional bioengineered organ
reconstructed by using an in vitro 3D cell culture is one of the successful goals in
regenerative medicine, which holds great promise for the replacement of dysfunc-
tional organs after disease, injury, or aging (Atala 2005 ; Purnell 2008 ). Organ
replacement by transplantation of bioengineered organ germ to restore the function
of damaged/lost ectodermal organs such as teeth, hair follicle, salivary glands, and
8 Functional Lacrimal Gland Regeneration