Cirrhosis is a long-term consequence of chronic hepatic injury and there are no effective treatment methods. Previous studies suggested that MSCs may ameliorate fibrogenesis through the inhibition of hepatic stellate cells (HSCs) activation. Previously we have reported that human liver-derived stem cells (HLSCs) could be isolated and expanded from donated liver not suitable for liver transplantation. HLSCs show mesenchymal morphology and grow well under serum conditions. Also they express some surface antigens of MSCs but are neither hematopoietic nor oval cells. When they are sequentially exposed to growth factors or cytokines they became round or polygonal and express hepatic markers, such as albumin, a-1-antitrypsin etc in the gene or protein level. The aim of this study was to assess the effectiveness of HLSCs in improving liver fibrosis.

Six week-old Sprague-Dawley rats were treated with carbon tetra-chloride (CCl4) by intraperitoneal injection twice a week for 8 weeks. Rats were injected with 1.2 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. HLSCs were injected into the rats through the portal vein after partial hepatectomy. After 4 weeks of HLSCs transplants, rats exhibited a significant reduction in liver fibrosis, as evidenced by Sirius Red staining, compared with rats without HLSCs transplants. Matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloprotease (TIMP) and transforming growth factor beta (TGFβ) were detected with real-time reverse transcriptase-polymerase chain reaction.

Biochemical and histopathological analyses showed significantly increased recovery from liver damage in the HLSCs transplanted group. In addition, HLSCs transplantation increased MMP-2, and decreased TIMP expression, and liver fibrosis was significantly decreased. HLSCs may stimulate MMP production in fibrotic livers, contributing to extracellular matrix (ECM) degradation and hepatic regeneration.

In conclusion, our data suggest that HLSCs may facilitate recovery from chronic liver damage and may decrease liverfibrosis by stimulating MMP production in a rat liver fibrosis model.

CITATION INFORMATION: Lee S, Lee J.-H, Park H.-J, Kim Y.-A, Park M.-N, Lee S.-K. The Therapeutic Potential of Human Liver-Derived Stem Cell Transplantation in a Cirrhotic Liver Rat Model. Am J Transplant. 2016;16 (suppl 3).

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