Article

Annals of Biomedical Engineering

, Volume 36, Issue 5, pp 865-876

Functional Modulation of ES-Derived Hepatocyte Lineage Cells via Substrate Compliance Alteration

  • Lulu LiAffiliated withDepartment of Chemical and Biochemical Engineering, Rutgers University
  • , Nripen SharmaAffiliated withDepartment of Chemical and Biochemical Engineering, Rutgers University
  • , Uday ChippadaAffiliated withDepartment of Mechanical and Aerospace Engineering, Rutgers University
  • , Xue JiangAffiliated withDepartment of Biomedical Engineering, Rutgers University
  • , Rene SchlossAffiliated withDepartment of Biomedical Engineering, Rutgers University
  • , Martin L. YarmushAffiliated withDepartment of Biomedical Engineering, Rutgers University
  • , Noshir A. LangranaAffiliated withDepartment of Mechanical and Aerospace Engineering, Rutgers UniversityDepartment of Biomedical Engineering, Rutgers University Email author 

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Abstract

Pluripotent embryonic stem cells represent a promising renewable cell source to generate a variety of differentiated cell types including hepatocyte lineage cells, and may ultimately be incorporated into extracorporeal bioartificial liver devices and cell replacement therapies. Recently, we and others have utilized sodium butyrate to directly differentiate hepatocyte-like cells from murine embryonic stem cells cultured in a monolayer configuration. However, to incorporate stem cell technology into clinical and pharmaceutical applications, and hopefully increase the therapeutic potential of these differentiated cells for liver disease treatment, a major challenge remains in sustaining differentiated functions for an extended period of time in their secondary culture environment. In the present work, we have investigated the use of polyacrylamide hydrogels with defined mechanical compliances as a cell culture platform for improving and/or stabilizing functions of these hepatocyte-like cells. Several functional assays, e.g., urea secretion, intracellular albumin content, and albumin secretion, were performed to characterize hepatic functions of cells on polyacrylamide gels with stiffnesses of 5, 46.6, and 230 kPa. In conjunction with the mechanical and cell morphological characterization, we showed that hepatic functions of sodium butyrate differentiated cells were sustained and further enhanced on compliant substrates. This study promises to offer insights into regulating stem cell differentiation via mechanical stimuli, and assist us with designing a variety of dynamic culture systems for applications in tissue and cellular engineering.

Keywords

Polyacrylamide hydrogels Substrate compliance Hepatocyte-like cells