![]() To date, five cellular liver assist devices (LADs) have been clinically tested and appear safe, 6– 12 but none have shown a survival benefit in ALF. Extracorporeal devices, by nature, are not implantable and circumvent the problem of immune rejection. ![]() Further, these approaches involve implantation of grafts and will encounter major immunological barriers, assuming a nonautologous cell source. 3 Tissue-engineered grafts 4, 5 have yet to be tested clinically, and it is unclear if the complex organ structure and function can be recapitulated in an artificial graft. Hepatocyte transplantation has been used to treat various liver diseases in over 25 patients and has been associated with partial improvements, but no significant correction of disease. These different approaches can be broadly classified as cell transplantation, tissue-engineered grafts, and cell-based extracorporeal devices. 2 Because the donor shortage is still limited, alternative approaches are under investigation to provide temporary support for patients as a bridge to transplantation or recovery.Ĭell-based technologies to support or artificially restore organ function represent one of the most promising avenues in the treatment of ALF. 1 Of larger clinical significance is acute-on-chronic liver failure where sudden insults can exacerbate chronic liver insufficiency. ALF Study Group (1998–2007), of the 44% of patients who were listed for transplantation, only 25% of the overall group received a graft and 10% died on the waiting list. These findings demonstrate the importance of nonparenchymal cells in the cellular composition of LADs, and strongly support the integration of MSCs into hepatocyte-coculture-based LADs as a potential destination therapy for ALF.Ī cute liver failure (ALF) affects approximately 2000 individuals annually in the United States, with mortality rates reportedly as high as 80% without successful liver transplantation. Moreover, MSC coculture reduced the overall cell mass of the device by an order of magnitude. Treatment with MSC-hepatocyte devices was associated with specific improvements in hepatic functional and histological parameters as well as decreasing inflammatory serum cytokine levels, validating a combined therapeutic effect. LADs containing cocultures of MSCs and hepatocytes provided a greater survival benefit compared to other coculture and monocellular control LADs. ![]() We then conducted a therapeutic trial of liver assist devices (LADs). In addition, we show that the MSC secretome is dynamically changed in response to serum exposure from ALF rats. MSCs were shown to have multiple beneficial effects in vitro that were relevant in a therapeutic context, including (1) hepatocellular functional support, (2) secretion of molecules that inhibit hepatocyte apoptosis, and (3) modulation of an acute phase response by hepatocytes cultured in ALF-induced serum. Here, we demonstrate the efficacy of MSCs, when cocultured with hepatocytes, to provide combination hepatic and antiinflammatory therapy in the setting of ALF. Recently, mesenchymal stem cells (MSCs) have been reported as a new therapeutic for inflammatory conditions. Cell-based technologies to support/restore organ function represent one of the most promising avenues in the treatment of acute liver failure (ALF). ![]()
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