Liver Tissue In Vitro (continued)

Cells in micropatterned co-cultures (click the picture to enlarge)

In these micropatterned co-cultures, heterotypic cell-cell interactions were varied while holding other key variables constant (i.e. cell numbers, ratio of cell populations, culture area, media volume, etc).

These studies demonstrated, for the first time to our knowledge, that identical cell populations when rearranged spatially can produce different levels of function in the resultant tissue.

Furthermore, immunohistochemical staining of the cultures for intracellular albumin (a marker of liver-specific protein synthesis) indicated that heterotypic signaling was limited to a few cells proximal to the

immunohistochemical staining (click the picture to enlarge)

heterotypic interface, and provided a rationale for varied levels of function exhibited by distinct tissue architectures. In the immunohistochemical staining image to the left, micropatterned hepatocytes alone (left) were compared to micropatterned co-cultures (right) by in situ staining for intracellular albumin (brown color). Note loss of staining in hepatocytes alone while staining is preserved in the vicinity of the heterotypic (fibroblast) interface in the latter image. The mechanisms of this cell-cell interaction are under investigation.

This finding will help to elucidate our observation that co-cultures with maximal interfacial regions functioned maximally. The molecular mechanisms by which these cell types interact to generate a highly functional tissue are currently under investigation- initial findings through a number of independent methods indicate that soluble factors are not sufficient to elicit the observed hepatocyte response .

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Research Interests

1. BioMEMS
   Our efforts have focused on the development of microtechnology tools for cell biology research and tissue engineering applications.

2. Hepatic Tissue Engineering
   We study the effects of the tissue microenvironment on the hepatocyte phenotype in vitro, for applications in cell-based therapies.