Abstract
Hepatic ischemia-reperfusion (I/R) injury is inevitable during hepatectomy and may cause both postoperative morbidity and mortality. Regenerative medicine suggested adipose-derived stem cells (ADSCs) as an attractive tool for the treatment of liver diseases. In this study, we investigated the effect of ADSCs in an I/R model combined with laparoscopic hepatectomy in swine. Eighteen Bama miniature pigs were randomly divided into Sham, IRI, and ADSCs groups. ADSCs (1 × 106/kg) were injected through liver parenchyma immediately after hemihepatectomy. The apoptosis-related role of ADSCs was studied. The results showed that ADSCs transplantation reduced both pathological and ultrastructural changes and decreased the number of apoptotic-positive cells. In the ADSCs group, Fas, Fas ligand (FasL) protein, and mRNA were downregulated and the enzyme activities of Caspase3, Caspase8, and Caspase9 were significantly decreased. In addition, ADSC therapy significantly increased the ratio of Bcl-2/Bax protein and mRNA compared to the IRI group. In conclusion, ADSCs attenuated both I/R and hepatectomy-induced liver apoptosis in a porcine model, and offers a potential therapeutic option for hepatic I/R and hepatectomy.
Highlights
Gagner et al and Reich et al reported the first laparoscopic hepatectomy during the early 1990s1,2
To investigate a prospective link to human adipose-derived stem cells (ADSCs) treatment of liver diseases, here, we investigated the anti-apoptotic effects of ADSCs in an I/R model combined with laparoscopic hepatectomy using a swine model
The expression of liver-specific genes such albumin (ALB), tyrosine aminotransferase (TAT), and hepatocyte nuclear factor 4 (HNF4) were not detected in passage 3 ADSCs; liver tissue was used as a positive control (Fig. 1I)
Summary
Gagner et al and Reich et al reported the first laparoscopic hepatectomy during the early 1990s1,2. I/R injury is an inevitable problem during hepatectomy and ischemia leads to the inhibition of oxidative phosphorylation, decreasing both ATP synthesis and intracellular pH levels. This may cause intracellular and mitochondrial calcium overload, inducing endoplasmic reticulum stress and necrosis. Only few animal models have been used for simultaneous I/R and hepatectomy injury, which is necessary to investigate a protective strategy in a model that combines I/R with hepatectomy[8,9,10,11]. To investigate a prospective link to human ADSC treatment of liver diseases, here, we investigated the anti-apoptotic effects of ADSCs in an I/R model combined with laparoscopic hepatectomy using a swine model
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