Korean J Hepatobiliary Pancreat Surg.  2011 May;15(2):107-116. 10.14701/kjhbps.2011.15.2.107.

Effect of Liver Cell Transplantation on Acute Hepatic Failure Induced by Massive Liver Resection in the Rat

• Park JH
• Yoon YC
• Hong TH
• You YK
• Kim DG

• KMID: 1980949
• DOI: http://doi.org/10.14701/kjhbps.2011.15.2.107

Abstract

PURPOSE
This study is designed to ascertain the most effective quantity and injection route of hepatocytes in an acute liver failure model induced by massive liver resection in rats.
METHODS
Rats weighing 450 to 650 gm underwent partial hepatectomy that was 80% of their liver weight, resulting in acute liver failure. Hepatocytes were obtained by perfusing collagenase (Wako, Japan) solution through portal vein into liver of the allogenic rat. These hepatocytes were injected into different places with different dosage. The experimental groups were divided into the Control group, Splenic group I (2x10(6) cells into splenic capsule), Splenic group II (2x10(7) cells into splenic capsule), Portal vein group (2x10(7) cells into portal vein), Subperitoneal group (2x10(7) cells into subperitoneum). The experimental animals were observed carefully for 5 days for assessment of survival and regeneration of liver. Liver function tests including serum alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (gamma-GTP) on postoperative 1, 2, 3, 5th days and histologic examinations of specimens obtained from each respective groups on postoperative 5th day were performed.
RESULTS
Serum ALT level on postoperative day 1 peaked and then gradually normalized showing statistical significance (p=0.035). Study groups showing statistically significant difference under repeated anova analysis were between the Splenic group II and Control (p=0.035), and between the Splenic group II and Portal vein group (p=0.001) with respect to serum ALT levels. Also, progression of each study group showed statistical significance. (p=0.02). Serum total bilirubin and r-GTP did not show any significant difference.
CONCLUSION
Hepatocyte transplantation of 2x10(7) cells into spleen showed the best results in the acute hepatic failure rat.

Keyword

Hepatocyte transplantation; Acute liver failure; Rat

MeSH Terms

Alanine Transaminase
Animals
Bilirubin
Cell Transplantation
Collagenases
Hepatectomy
Hepatocytes
Liver
Liver Failure, Acute
Liver Function Tests
Portal Vein
Rats
Regeneration
Spleen
Transferases
Transplants
Alanine Transaminase
Bilirubin
Collagenases
Transferases

Figure

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  Fig. 1 Operative findings after massive resection of liver (arrow head: right superior lobe and omental lobe).

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  Fig. 2 Operative view of canulation in portal vein (A), infusion of collagenase solution with whitish discoloration of liver (B) and resected liver after collagenase perfusion (C).

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  Fig. 3 Hepatocyte in trypan blue exclusion test (×200).

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  Fig. 4 The change of alanine aminotransferase (ALT) level according to each groups.

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  Fig. 5 The change of total bilirubin level according to each groups.

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  Fig. 6 The change of gamma-glutamyl transferase (γ-GTP) level according to each groups.

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  Fig. 7 Histologic feature of hepatocyte of each groups on the day of sacrifice. (A) Liver of control group (HE staining, ×400), (B) colonization of the irregular sheets of transplanted hepatocyte in spleen group II (some of which show degenerative feature) (HE staining ×200 and ×400), (C) transplanted hepatocyte in portal vein and occlusion of smaller portal branch on portal vein group, (HE staining ×400), (D) colonization of transplanted hepatocyte between subperitoneal fat tissues on subperitoneal group (HE staining, ×200), (arrow: hepatocytes & red cells in portal vein branch).

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