Control of hepatic differentiation via cellular aggregation in an alginate microenvironment

Tim Maguire, Alexander E. Davidovich, Eric J. Wallenstein, Eric Novik, Nripen Sharma, Henrik Pedersen, Ioannis P. Androulakis, Rene Schloss, Martin Yarmush

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Integral to the development of embryonic stem cell therapeutic strategies for hepatic disorders is the identification and establishment of a controllable hepatic differentiation strategy. In order to address this issue we have established an alginate microencapsulation approach which provides a means to modulate the differentiation process through changes in key encapsulation parameters. We report that a wide array of hepatocyte specific markers is expressed by cells differentiated during a 23-day period within an alginate bead microenvironment. These include urea and albumin secretion, glycogen storage, and cytochrome P450 transcription factor activity. In addition, we demonstrate that cellular aggregation is integral to the control of differentiation within the bead environment and this process is mediated by the E-cadherin protein. The temporal expression of surface E-cadherin and hepatocyte functional expression occur concomitantly and both cellular aggregation and albumin synthesis are blocked in the presence of anti E-cadherin immunoglobulin. Furthermore, by establishing a compartmental model of differentiation, which incorporates this aggregation phenomenon, we can optimize key encapsulation parameters.

Original languageEnglish (US)
Pages (from-to)631-644
Number of pages14
JournalBiotechnology and Bioengineering
Volume98
Issue number3
DOIs
StatePublished - Oct 15 2007

All Science Journal Classification (ASJC) codes

  • Applied Microbiology and Biotechnology
  • Bioengineering
  • Biotechnology

Keywords

  • Alginate
  • Differentiation
  • Embryonic stem cells
  • Encapsulation
  • Hepatocytes

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