Brief Article
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World J Gastroenterol. Feb 21, 2011; 17(7): 938-945
Published online Feb 21, 2011. doi: 10.3748/wjg.v17.i7.938
Transplantation of microencapsulated umbilical-cord-blood-derived hepatic-like cells for treatment of hepatic failure
Fang-Ting Zhang, Hui-Juan Wan, Ming-Hua Li, Jing Ye, Mei-Jun Yin, Chun-Qiao Huang, Jie Yu
Fang-Ting Zhang, Hui-Juan Wan, Ming-Hua Li, Jing Ye, Mei-Jun Yin, Chun-Qiao Huang, Jie Yu, Central Laboratory, Peking University Shenzhen Hospital, Shenzhen 518036, China
Author contributions: Zhang FT and Yu J designed the research; Zhang FT, Wan HJ, Li MH, Yin MJ, Ye J and Huang CQ performed the research; Zhang FT analyzed data; Zhang FT wrote the paper; Yu J edited the paper.
Supported by Guangdong Natural Science Foundation (9151030002000008) and Shenzhen Science and Technology Planning Priority Program (JH200205270412B, 200808001, 200801012)
Correspondence to: Jie Yu, PhD, Central Laboratory, Peking University Shenzhen Hospital, 1120 Lian Hua Road, Shenzhen 518036, China.
Telephone: +86-755-83923333 Fax: +86-755-83923333
Received: July 19, 2010
Revised: October 20, 2010
Accepted: October 27, 2010
Published online: February 21, 2011

AIM: To investigate intraperitoneal transplantation of microencapsulated hepatic-like cells from human umbilical cord blood for treatment of hepatic failure in rats.

METHODS: CD34+ cells in umbilical cord blood cells were isolated by magnetic cell sorting. In the in vitro experiment, sorted CD34+ cells were amplified and induced into hepatic-like cells by culturing with a combination of fibroblast growth factor 4 and hepatocyte growth factor. Cultures without growth factor addition served as controls. mRNA and protein levels for hepatic-like cells were analyzed by reverse transcription-polymerase chain reaction, immunohistochemistry and immunofluorescence. In the in vivo experiment, the hepatic-like cells were encapsulated and transplanted into the abdominal cavity of acute hepatic failure (AHF) rats at 48 h after D-galactosamine induction of acute hepatic failure. Transplantation with PBS and unencapsulated hepatic-like cells served as controls. The mortality rate, hepatic pathological changes and serum biochemical indexes were determined. The morphology and structure of microcapsules in the greater omentum were observed.

RESULTS: Human albumin, alpha-fetoprotein and GATA-4 mRNA and albumin protein positive cells were found among cultured cells after 16 d. Albumin level in culture medium was significantly increased after culturing with growth factors in comparison with culturing without growth factor addition (P < 0.01). Compared with the unencapsulated group, the mortality rate of the encapsulated hepatic-like cell-transplanted group was significantly lower (P < 0.05). Serum biochemical parameters, alanine aminotransferase, aspartate aminotransferase and total bilirubin in the encapsulated group were significantly improvement compared with the PBS control group (P < 0.01). Pathological staining further supported these findings. At 1-2 wk post-transplantation, free microcapsules with a round clear structure and a smooth surface were observed in peritoneal lavage fluid, surviving cells inside microcapsules were found by trypan blue staining, but some fibrous tissue around microcapsules was also detected in the greater omentum of encapsulated group by hematoxylin and eosin staining.

CONCLUSION: Transplantation of microencapsulated hepatic-like cells derived from umbilical cord blood cells could preliminarily alleviate the symptoms of AHF rats.

Keywords: Microencapsulation, Hepatic-like cells, Umbilical cord blood cells, CD34 antigen, Alginate, Acute hepatic failure