Transplantation of side population cells restores the function of damaged exocrine glands through clusterin.
Stem cell-based therapy has been proposed as a promising strategy for regenerating tissues lost through incurable diseases. Side population (SP) cells have been identified as putative stem cells in various organs. To examine therapeutic potential of SP cells in hypofunction of exocrine glands, SP cells isolated from mouse exocrine glands, namely, lacrimal and salivary glands, were transplanted into mice with irradiation-induced hypofunction of the respective glands. The secretions from both glands in the recipient mice were restored within 2 months of transplantation, although the transplanted cells were only sparsely distributed and produced no outgrowths. Consistent with this, most SP cells were shown to be CD31-positive endothelial-like cells. In addition, we clarified that endothelial cell-derived clusterin, a secretory protein, was an essential factor for SP cell-mediated recovery of the hypofunctioning glands because SP cells isolated from salivary glands of clusterin-deficient mice had no therapeutic potential, whereas lentiviral transduction of clusterin restored the hypofunction. In vitro and in vivo studies showed that clusterin had an ability to directly inhibit oxidative stress and oxidative stress-induced cell damage. Thus, endothelial cell-derived clusterin possibly inhibit oxidative stress-induced hypofunction of these glands.
Department of Pathology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Japan.
Kenji
K
Mishima
Hiroko
H
Inoue
Tatsuaki
T
Nishiyama
Yo
Y
Mabuchi
Yusuke
Y
Amano
Fumio
F
Ide
Makoto
M
Matsui
Hiroyuki
H
Yamada
Gou
G
Yamamoto
Junichi
J
Tanaka
Rika
R
Yasuhara
Takashi
T
Sakurai
Masaichi-Chang-Il
MC
Lee
Kan
K
Chiba
Hidetoshi
H
Sumimoto
Yutaka
Y
Kawakami
Yumi
Y
Matsuzaki
Kazuo
K
Tsubota
Ichiro
I
Saito
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000235:genetics; D051152:Clusterin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D007765:Lacrimal Apparatus / Q000166:cytology / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000502:physiology*; D058985:Side-Population Cells / Q000502:physiology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods*
D000950:Antigens, Ly; D051152:Clusterin; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017382:Reactive Oxygen Species