Hepatocyte transplantation from steatotic liver in a rat model.
BACKGROUND
Hepatocyte transplantation (HTx) has progressed significantly, but widespread application remains slow because of the shortage of donor hepatocytes. Many sources of hepatic cells have been proposed as alternatives to isolated hepatocytes, but primary isolated hepatocytes continue to be the best source for liver cell-based therapy. To expand the donor pool, we focused on steatotic liver as a new cell source for HTx because numerous steatotic livers are discarded as unsuitable for orthotopic liver transplantation. This study investigated the efficacy of steatotic hepatocyte transplantation (SHTx) using steatotic liver in a rat model.


METHODS
Hepatocytes were isolated from obese and lean Zucker rats. Hepatocytes from each group were cultured to analyze the function of steatotic hepatocytes. Hepatocytes from each group were also transplanted into the spleens of Nagase analbuminemic rats (NARs) to investigate the efficacy of SHTx.


RESULTS
In the in vitro experiment, a real-time reverse-transcription polymerase chain reaction assay showed that albumin and several hepatocyte nuclear factors were highly expressed in both groups. Morphologically, the steatotic hepatocytes were positive for albumin, and an enzyme-linked immunosorbent assay showed no significant differences between the two groups except for albumin production after 5 d of culture. In the in vivo experiment, the transplanted steatotic hepatocytes in the spleens of Nagase analbuminemic rats were positive for albumin and periodic acid-Schiff staining. Surprisingly, an enzyme-linked immunosorbent assay showed no significant differences in the serum albumin levels between the two groups throughout the study period.


CONCLUSIONS
We have demonstrated that steatotic hepatocytes are a potential new cell source for HTx therapy.
Hayashi
Ken
K
Division of General and Gastroenterological Surgery, Department of Surgery, School of Medicine, Showa University, Tokyo, Japan.
Aoki
Takeshi
T
Jin
Zhenghao
Z
Wang
Hexian
H
Nishino
Nobukazu
N
Kusano
Tomokazu
T
Yasuda
Daisuke
D
Koizumi
Tomotake
T
Enami
Yuta
Y
Odaira
Masanori
M
Yamada
Kousuke
K
Mitamura
Keitaro
K
Niiya
Takashi
T
Murai
Noriyuki
N
Kato
Hirohisa
H
Shimizu
Yoshinori
Y
Kusano
Mitsuo
M
D000418:Albumins / Q000378:metabolism; D000818:Animals; D017690:Cell Transplantation / Q000379:methods* / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology* / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D014508:Urea / Q000378:metabolism
D000418:Albumins; D014508:Urea