Intrasplenic transplantation of encapsulated hepatocytes decreases mortality and improves liver functions in fulminant hepatic failure from 90% partial hepatectomy in rats.
BACKGROUND
Encapsulated cell therapy might be a promising approach to enable cell transplantation without immunosuppression. This study investigates the viability and hepatic function of hepatocytes encapsulated with alginate/poly-L-lysine in vitro and the effect of the intrasplenic transplantation of cultured encapsulated hepatocytes on survival in 90% hepatectomized rats as a preliminary step toward allogeneic hepatocyte transplantation without immunosuppression.


METHODS
Rat hepatocytes were isolated and encapsulated using alginate/poly-L-lysine. Encapsulated hepatocytes were cultured for 28 days to measure cell viability, liver function, and morphology. Rats were treated with a 90% partial hepatectomy and then immediately underwent the intrasplenic transplantation of the cultured encapsulated hepatocytes, the capsule alone, or the allogeneic hepatocytes without the capsule. The survival rate, liver function, and cell morphology were assessed after transplantation.


RESULTS
The cultured encapsulated hepatocytes maintained their viability and showed better metabolic activity than day 0 cultured encapsulated hepatocytes. The encapsulated cells strongly expressed albumin and were positive for periodic acid-Schiff staining. Electron microscopy demonstrated that the microencapsulated hepatocytes retained the structural elements of hepatic cytoplasm and nuclei. Intrasplenic transplantation of the encapsulated hepatocytes increased the survival rate and improved the hepatic function. Encapsulated hepatocytes transplanted into rat spleen survived well and retained their hepatic function. Moreover, dramatic liver regeneration was observed 48 hr after transplantation in the group that received intrasplenic transplantations of encapsulated hepatocytes.


CONCLUSIONS
The intrasplenic transplantation of cultured encapsulated hepatocytes improved the survival rate of an acute liver failure rat model induced by a 90% partial hepatectomy.
Aoki
Takeshi
T
Division of General and Gastroenterological Surgery, Department of Surgery, School of Medicine, Showa University, Tokyo, Japan. takejp@wb4.so-net.ne.jp
Jin
Zhenghao
Z
Nishino
Nobukazu
N
Kato
Hirohisa
H
Shimizu
Yoshinori
Y
Niiya
Takashi
T
Murai
Noriyuki
N
Enami
Yuta
Y
Mitamura
Keitaro
K
Koizumi
Tomotake
T
Yasuda
Daisuke
D
Izumida
Yoshihiko
Y
Avital
Izhak
I
Umehara
Yutaka
Y
Demetriou
Achilles A
AA
Rozga
Jacek
J
Kusano
Mitsuo
M
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000637:transplantation* / Q000648:ultrastructure; D017114:Liver Failure, Acute / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration; D046529:Microscopy, Electron, Transmission; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen; D015996:Survival Rate; D014184:Transplantation, Homologous