Abstract
Mesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therapies for acute liver failure (ALF). The cotransplantation of hepatocytes with MSCs can improve the therapeutic performance for the treatment of ALF. However, the therapeutic potential of conditioned medium (CM) derived from MSCs cocultured with hepatocytes (MSC-H-CM) remains unclear. The purpose of this study was to investigate the effects of MSC-H-CM on damaged hepatocytes in vitro and on D-galactosamine-induced ALF in vivo. D-Galactosamine-treated L02 cells cultured in MSC-H-CM exhibited higher of cell viability and total protein synthesis than L02 cells cultured in MSC-CM, CM derived from hepatocytes (H-CM), MSC-CM + H-CM, or with nonconditioned medium (NCM). Lactate dehydrogenase and aspartate aminotransferase levels were lower in the supernatant of damaged L02 cells cultured in MSC-H-CM than in that of L02 cells cultured in other types of CM. The lowest percentage of apoptotic cells was observed after the MSC-H-CM treatment. When CM was injected into the tail vein of rats with ALF, MSC-H-CM was the most successful at preventing the release of liver injury biomarkers and in promoting the recovery of liver structure. The greatest survival rate 7 days after the first treatment was observed in the MSC-H-CM-treated rats. Our results reveal that the delivery of MSC-H-CM could be a novel strategy for integrating the therapeutic potentials of hepatocytes and MSCs for the treatment of ALF.
Highlights
Liver transplantation is the only long-term effective treatment for acute liver failure (ALF), but it is limited by the shortage of transplantable organs [1]
Among hepatocytes cocultured with mesenchymal stem cells (MSCs), there were a large number of polyhedral cells with well-demarcated cell-cell borders, distinct nuclei, and binucleate, which are typical morphological features of hepatocytes (Figure 1(d))
Paracrine factors derived from MSCs are primarily responsible for the beneficial effects of cell-based therapies in the treatment of ALF [13, 14]
Summary
Liver transplantation is the only long-term effective treatment for acute liver failure (ALF), but it is limited by the shortage of transplantable organs [1]. With the advancement of regenerative medicine, alternatives to liver transplantation are becoming distinct possibilities—be it through hepatocyte transplantation, stem cell therapy, or tissue-engineered grafts [2,3,4]. The liver is amenable to these cell-based therapies due to its innate capacity for intense regeneration and self-repair [5]. Cell-based therapies have been proposed as a promising avenue for bridging a patient to either liver transplantation or to native liver recovery through endogenous regeneration [2]. Hepatocytes and mesenchymal stem cells (MSCs) are two attractive sources of cell-based therapies for ALF. Previous studies have demonstrated that hepatocyte transplantation can compensate for liver dysfunction, which plays an important role in cell-based therapies for ALF [6].
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