Clin Mol Hepatol.  2015 Jun;21(2):141-149. 10.3350/cmh.2015.21.2.141.

Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis

• Jang YO
• Jun BG
• Baik SK
• Kim MY
• Kwon SO

• KMID: 2164364
• DOI: http://doi.org/10.3350/cmh.2015.21.2.141

Abstract

BACKGROUND/AIMS
Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.
METHODS
We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (alpha-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.
RESULTS
The BM-MSCs in the direct co-culture system significantly decreased the production of alpha-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-beta1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of alpha-SMA and inducing the apoptosis of HSCs.
CONCLUSIONS
These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

Keyword

Bone-marrow-derived mesenchymal stem cell; Cirrhosis; Hepatic fibrosis

MeSH Terms

Apoptosis
Bone Marrow Cells/*cytology
Cell Differentiation
Coculture Techniques
Hepatic Stellate Cells/*cytology/metabolism
Hepatocyte Growth Factor/metabolism
Humans
Immunophenotyping
Interleukin-10/metabolism
Interleukin-6/metabolism
Liver Cirrhosis
Mesenchymal Stromal Cells/*cytology/metabolism
Transforming Growth Factor beta1/metabolism
Hepatocyte Growth Factor
Interleukin-10
Interleukin-6
Transforming Growth Factor beta1