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Review
, 30 (5), 580-9

Mesenchymal Stem Cell Therapy for Liver Fibrosis

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Review

Mesenchymal Stem Cell Therapy for Liver Fibrosis

Young Woo Eom et al. Korean J Intern Med.

Abstract

Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.

Keywords: Anti-fibrosis; Immune modulation; Liver cirrhosis; Mesenchymal stromal cells; Trophic factors.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Figure 1.
Figure 1.
Potential roles of mesenchymal stem cells (MSCs) in liver fibrosis. Liver fibrosis is initiated by hepatic injury and the subsequent imbalance of extracellular matrix (ECM) synthesis and degradation mediated by activated hepatic stellate cells (HSCs). Potential protective mechanisms of MSCs include the following: (1) trans-differentiation into hepatocyte-like cells; (2) suppression of immune reactions; (3) secretion of trophic factors to suppress activated HSCs and increase the proliferation of both resident hepatocytes and hepatic progenitor cells; and (4) anti-fibrosis resulting from the regulation of activated HSCs and immune cells. Solid lines and dashed lines indicate stimulatory and inhibitory modifications, respectively. The + sign represents tentative stimulatory effects. The shadows represent ECM that is secreted from the HSCs. NO, nitric oxide; PGE2, prostaglandin E2; IDO, indoleamine 2,3-dioxygenase; IL, interleukin; HLA-G, human leukocyte antigen G; PD, programmed death; DC, dendritic cell; NK, nature killer; Treg, regulatory T; HGF, hepatocyte growth factor; NGF, nerve growth factor; TNF-α, tumor necrosis factor α; EGF, epidermal growth factor; TGF-α, transforming growth factor α; VEGF, vascular endothelial growth factor.

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