- 作者：Hironobu Amano M.D.* ; Hiroshi Hino M.D.* ; Chise Tateno Ph.D.† ; ; Kentaro Emoto M.D.* ; Yasuhiro Imaoka M.D.* ; Chihiro Yamasaki Ph.D.‡ ; ; Toshiyuki Itamoto M.D.* ; Hirotaka Tashiro M.D.* ; Toshimasa Asahara M.D.* ; Hideki Ohdan M.D.* ; Katsutoshi Yoshizato Ph.D.† ; ; ‡ ; ; § ; ; katsutoshi.yoshizato@phoenixbio.co.jp
- 关键词：dipeptidyl peptidase IV mutant rats ; intrasplenic transplantation ; omental lobe ; apoptosis ; histopathology ; hepatectomy
- 刊名：Journal of Surgical Research
- 出版年：2011
- 出版时间：1 May 2011
- 年：2011
- 卷：167
- 期：1
- 页码：e29-e37
- 全文大小：1127 K
Background
This study aimed to evaluate the therapeutic potential of intrasplenic transplantation of culture-propagated homologous hepatocytes in rats suffering from acute liver failure (ALF).Methods
ALF was induced in dipeptidyl peptidase IV-negative (DPPIV−) Fischer 344 rats by totally removing the two anterior liver lobes (68 % of the liver) and ligating the pedicle of the right lobe (24 % of the liver). Hepatocytes isolated from DPPIV+ Fischer 344 rats were cultured for 11 d to propagate 3-fold, and the resulting hepatocytes were dubbed “culture-propagated hepatocytes (CPHEPs)”. A total of 1.5 × 107 cells of CPHEPs were transplanted intrasplenically before ALF induction (CPHEP group). Similarly, freshly isolated hepatocytes (FIHEPs) were transplanted as a positive control (FIHEP group), and culture medium (CM) was injected into rats as a negative control (CM group).
Results
The survival of the CPHEP group was comparable to that of the FIHEP group and longer than that of the CM group (P < 0.01). Both CPHEP and FIHEP transplantation improved blood parameters such as ammonia, total bilirubin, glutamic pyruvic transaminase, and glutamic oxaloacetic transaminase; transplantation also affected liver tissue parameters such as apoptosis rate and bromodeoxyuridine-labeling index.
Conclusions
Transplantation of culture-propagated homologous hepatocytes has a remarkable therapeutic potential for ALF in rats.