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Liver-Specific Maturation Behavior of Cadherin Expressing Embryonic Stem Cells Microspatially Cocultured with Mature Hepatocytes

Prabhas W. Moghe, Rutgers University, Department of Biomedical Engineering; Department of Chemical & Biochemical Engineering); Director, Rutgers NSF IGERT Program on Biointerfaces.
 

Collaborative Project #5, entitled " Liver-Specific Maturation Behavior of Cadherin Expressing Embryonic Stem Cells Microspatially Cocultured with Mature Hepatocytes" is led by Dr. Prabhas V. Moghe in the Department of Biomedical Engineering at Rutgers University.

The main goal of our collaborative effort is to investigate the hepatodifferentiation behavior of cadherin expressing ES cells within a microengineered organotypic model comprising co-cultures of ES cells and adult hepatocytes.

Our major hypothesis is that mature hepatocytes can induce hepatospecific maturation of primed ES cells via two primary mechanisms related to cadherin signaling: juxtacrine signaling (initiated through cadherin-cadherin contacts between CE-ES and hepatocytes) and paracrine signaling (distally initiated by hepatocytes; mediated by cadherin growth factor signaling pathways).

In our earlier coculture studies, we showed that both of these mechanisms were important for the differentiation of hepatocytes. Currently we are investigating the coupled juxtacrine-paracrine signaling between hepatocytes and ES cells using micropatterned hepatocytes within the micro-islands utilizing customized stencils microfabricated by the BioMEMS resource Center at MGH. Early results suggest that direct cadherin-based contacts between hepatocytes and ES cells are instrumental in promoting ES cell hepatodifferentiation.



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