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Posted: Sep 25, 2013

Engineering liver tissue from embryonic stem cells

(Nanowerk News) The liver, an essential organ, can fail due to disease or abuse. The EU-funded project MICROLIVERMATURATION has found a way to create viable liver cells from embryonic stem cells (ESCs).
Unlike adult stem cells, ESCs (obtained from embryos) can differentiate into any desired cell or tissue type. However, in the case of engineered liver cells (also called hepatocytes) there are several issues complicating the process, such as mixed cell populations, minimal metabolic function and long-term de-differentiation. 'Gene network-based maturation of embryonic stem cell-derived hepatocytes in a microfabricated array' (MICROLIVERMATURATION) is an EU-funded project that aims to resolve these issues.
MICROLIVERMATURATION researchers started out with the premise that modulating transcription factor activity could make the differentiated hepatocytes similar to mature hepatocytes. Keeping this in mind, scientists developed and optimised a protocol for differentiating ESCs into hepatocytes. For this purpose, they used an advanced microfluidic device called Living Cell Array (LCA). LCA has multiple green fluorescent protein (GFP) reporter libraries for screening, monitoring, understanding and controlling transcriptional events.
Project scientists successfully developed and optimised a 16-day protocol that is reproducible. Viable immature foetal-like hepatocytes expressing alpha-fetoprotein (AFP) and albumin were generated. These cells were highly homogenous and similar to human hepatocytes with albumin production reaching 5 microgram/day/million cells. Three natural agonists, compounds that bind to receptors and activate biological response, were identified. These play a critical role in transcription factor activity and metabolic maturation of the cells.
Successful project outcomes to date have to some extent elucidated the role of nutrition in the maturation of neonatal cells to mature hepatocytes. These findings could result in several clinical applications and novel pharmaceutical drug developments.
Source: Cordis
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