Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells on Concanavalin A-Induced Acute Liver Injury in Mice.
Cell therapy with adipose tissue-derived stem cells (ASCs) is expected to be a candidate for the treatment of fulminant hepatic failure (FHF), which is caused by excessive immune responses. In order to evaluate the therapeutic effects of ASCs on FHF, the in vitro and in vivo immunomodulatory effects of ASCs were examined in detail in the mouse model. The in vitro effects of ASCs were examined by assessing their influence on the proliferation of lymphomononuclear cells (LMCs) stimulated with three kinds of mitogens: phorbol 12-myristate 13-acetate (PMA) plus ionomycin, concanavalin A (ConA), and lipopolysaccharide (LPS). The proliferation of LMCs was efficiently suppressed in a dose-dependent manner by ASCs in the cases of PMA plus ionomycin stimulation and ConA stimulation, but not in the case of LPS stimulation. The in vivo effects of transplanted ASCs were examined in the murine FHF model induced by ConA administration. The ALT levels and histological inflammatory changes in the ConA-administered mice were apparently relieved by the transplantation of ASCs. The analysis of mRNA expression patterns in the livers indicated that the expressions of the cytokines such asIl-6,Il-10,Ifn-γ, andTnf-α, and the cell surface markers such asCd3γ,Cd4,Cd8α,Cd11b, andCd11cwere downregulated in the ASC-transplanted mice. The immunomodulatory and therapeutic effects of ASCs were confirmed in the mouse model both in vitro and in vivo. These suggest that the cell therapy with ASCs is beneficial for the treatment of FHF.
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Yasuma
Y
Yoshizumi
†ImPACT Research Center for Innovative Nanobiodevices, Nagoya University, Chikusa-ku, Nagoya, Japan; ‡Department of Applied Chemistry, Nagoya University Graduate School of Engineering, Chikusa-ku, Nagoya, Japan.
Hiroshi
H
Yukawa
§ Kinuura-Tobu Health Care Center , Kariya , Japan.
Ryoji
R
Iwaki
¶ Department of Clinical Laboratories, Aichi Cancer Center Hospital , Chikusa-ku, Nagoya , Japan.
Sanae
S
Fujinaka
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Ayano
A
Kanou
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Yuki
Y
Kanou
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Tatsuya
T
Yamada
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Shingo
S
Nakagawa
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Tomomi
T
Ohara
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Kenta
K
Nakagiri
‡ Department of Applied Chemistry, Nagoya University Graduate School of Engineering , Chikusa-ku, Nagoya , Japan.
Yusuke
Y
Ogihara
† ImPACT Research Center for Innovative Nanobiodevices, Nagoya University , Chikusa-ku, Nagoya , Japan.
Yoko
Y
Tsutsui
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Yumi
Y
Hayashi
# Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya , Japan.
Masatoshi
M
Ishigami
†ImPACT Research Center for Innovative Nanobiodevices, Nagoya University, Chikusa-ku, Nagoya, Japan; ‡Department of Applied Chemistry, Nagoya University Graduate School of Engineering, Chikusa-ku, Nagoya, Japan.
Yoshinobu
Y
Baba
Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , Higashi-ku, Nagoya , Japan.
Tetsuya
T
Ishikawa
Adipose tissue-derived stem cells (ASCs); Concanavalin A (Con A); Fulminant hepatic failure (FHF); Immunomodulatory effect