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<p>Mortality and morbidity rates caused by acute liver failure (ALF), acute-on-chronic
liver failure (ACLF) and chronic liver disease continue to rise because of drug induced
failure or viral hepatitis, currently with 2,000 cases annually in the United States.
Liver transplantation is the only intervention that has shown the most promising patient
outcomes, but this approach has major shortcomings like shortage of donor livers,
lifelong immunosuppression and a risk of organ rejection after transplantation. Additionally,
with rapid liver deterioration and subsequent multi-organ failure characterized by
ALF and ACLF conditions, there are high mortality rates as patients await a liver
transplant or wait for their livers to regenerate. As such, bioartificial liver support
devices provide an alternative to improve patient survival through either offloading
liver functions to allow for liver regeneration or by allowing the patient time to
receive a liver transplant. These bioartificial liver support devices are designed
to perform essential liver functions through incorporation of an active cellular component
that performs the liver functions and their success is therefore heavily reliant on
the performance of the incorporated cell lines. Because of this, limited sources of
these characteristic cell lines with hepatic function is a great challenge being faced
in the research and development of the devices. </p><p> </p><p>Adipose-derived stem
cells (ADSCs) are a great candidate as a stem cell source for differentiation of hepatocyte-like
cells because they can be easily obtained in large quantities with little donor site
morbidity or discomfort and have been successfully differentiated into multiple cell
lineages. In this study, we investigate the possibility of differentiating human ADSCs
into functional hepatocyte-like cells. Furthermore, we investigated the ability to
differentiate ADSCs into hepatocyte-like cells in both 2D and 3D environments. We
found that induced ADSCs can produce high levels of some hepatocyte functions, like
albumin secretion. However, other functions, like urea secretion and cytochrome P450
metabolic activity, while present, are not yet at sufficient levels to be comparable
to primary hepatocytes.</p>
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