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J Surg Res. 2013 Dec;185(2):889-95. doi: 10.1016/j.jss.2013.06.016. Epub 2013 Jun 29.

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells.

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1
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Abstract

BACKGROUND:

The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells.

MATERIALS AND METHODS:

First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 10(7). Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells.

RESULTS:

Sixteen weeks after transplantation, the donor cells constituted > 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed.

CONCLUSIONS:

HIR, combined with PVBL, can be given to a selective liver lobe and is a less-invasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.

KEYWORDS:

Adipose-derived mesenchymal stem cell; Hepatic irradiation; Hepatocyte transplantation; Portal vein branch ligation; Small hepatocyte

PMID:
23845872
DOI:
10.1016/j.jss.2013.06.016
[Indexed for MEDLINE]
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