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Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Abstract

Mesenchymal stem (stromal) cells (MSCs) are a source of circulating progenitors that are able to generate cells of all mesenchymal lineages and to cover cellular demands of injured tissues. The extent of their transdifferentiation plasticity remains controversial. Cells with MSC properties have been obtained from diverse tissues after purification and expansion in vitro. These cellular populations are heterogeneous and under certain conditions show pluripotent-like properties. MSCs present immunosuppressive and anti-inflammatory features and high migratory capacity toward inflamed or remodeling tissues. In this study we review available data regarding factors and signaling axes involved in the chemoattraction and engraftment of MSCs to an injured tissue or to a tissue undergoing active remodeling. Moreover, experimental evidence in support of uses of MSCs as vehicles of therapeutic genes is discussed. Because of its regenerative capacity and its particular immune properties, the liver is a good model to analyze the potential of MSC-based therapies. Finally, the potential application of MSCs and genetically modified MSCs in liver fibrosis and hepatocellular carcinoma (HCC) is proposed in view of available evidence.

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Acknowledgements

This study was supported in part by grants from Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (PICT 2005 34788 (GM), PICTO-CRUP 2005 31179 (GM), AECI 2008 D/022066/08 (GM); PICT-PAE 00085 to MB, 00082 to MG, 00221 to OP; PRH 2007 No. 51). JBA is also supported by a grant from Austral University.

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Aquino, J., Bolontrade, M., García, M. et al. Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma. Gene Ther 17, 692–708 (2010). https://doi.org/10.1038/gt.2010.10

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