Endothelial progenitor cell transplantation improves the survival following liver injury in mice.
OBJECTIVE
Neovascularization, which is vital to the healing of injured tissues, recently has been found to include both angiogenesis, which involves in mature endothelial cells, and vasculogenesis, involving endothelial progenitor cells. The aim of this study was to clarify the possible roles of endothelial progenitor cells during postnatal liver regeneration.


METHODS
To determine how endothelial progenitor cells participate in liver regeneration, human or mouse endothelial progenitor cells were transplanted into the mice with carbon tetrachloride-induced acute liver injury. Survival rate of the mice in endothelial progenitor cell-transplanted and control groups was calculated. Separately, livers removed temporally from both groups were examined.


RESULTS
At an early stage, transplanted human endothelial progenitor cells were seen mainly surrounding hepatic central veins where hepatocytes showed extensive necrosis; later, the transplanted cells formed tubular structures. More of these cells were observed along hepatic sinusoids. Transplantation of human or mouse endothelial progenitor cells improved survival of the mice following liver injury (from 28.6% to 85.7%, P < .0005 and from 33.3% to 80.0%, P < .001, respectively), accompanied by greater proliferation of hepatocytes. Human endothelial progenitor cells produced several growth factors, such as hepatocyte growth factor, transforming growth factor-alpha, heparin-binding epidermal growth factor-like growth factor, and vascular endothelial growth factor, and also elicited endogenous growth factors.


CONCLUSIONS
Endogenous and exogenous growth factors and direct neovascularization after endothelial progenitor cell transplantation promoted liver regeneration, thus improving survival after liver injury. Transplantation of endothelial progenitor cells could represent a new therapeutic strategy for promoting liver regeneration.
Second Department of Medicine, Kurume University School of Medicine, Liver Cancer Division, Research Center for Innovative Cancer Therapy of the 21st Century COE Program for Medical Science, Japan. eitaro@med.kurume-u.ac.jp
Eitaro
E
Taniguchi
Motoaki
M
Kin
Takuji
T
Torimura
Toru
T
Nakamura
Hiroto
H
Kumemura
Shinichiro
S
Hanada
Takao
T
Hisamoto
Takafumi
T
Yoshida
Takumi
T
Kawaguchi
Shinji
S
Baba
Michiko
M
Maeyama
Hironori
H
Koga
Masaru
M
Harada
Ryukichi
R
Kumashiro
Takato
T
Ueno
Shinya
S
Mizuno
Hisao
H
Ikeda
Tsutomu
T
Imaizumi
Toyoaki
T
Murohara
Michio
M
Sata
D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000196:embryology / Q000637:transplantation*; D006801:Humans; D008099:Liver / Q000293:injuries* / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D016019:Survival Analysis