Maturation of induced pluripotent stem cell derived hepatocytes by 3D-culture.

PLoS One

Wellcome Trust-Medical Research Council Stem Cell Institute, Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom ; Wellcome Trust Sanger Institute, Hinxton, United Kingdom.

Published: November 2014

AI Article Synopsis

  • Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) show promise for applications in cell therapy and toxicology but currently exhibit reduced functionality compared to adult liver cells.
  • A new 3D collagen matrix culture method enhances the maturation of IPSC-Heps, achieving a more adult-like phenotype and increasing their functional capacity.
  • This innovative approach also supports the formation of essential polarized structures for drug metabolism and significantly extends the viability of these cells beyond 75 days.

Article Abstract

Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) have the potential to reduce the demand for a dwindling number of primary cells used in applications ranging from therapeutic cell infusions to in vitro toxicology studies. However, current differentiation protocols and culture methods produce cells with reduced functionality and fetal-like properties compared to adult hepatocytes. We report a culture method for the maturation of IPSC-Heps using 3-Dimensional (3D) collagen matrices compatible with high throughput screening. This culture method significantly increases functional maturation of IPSC-Heps towards an adult phenotype when compared to conventional 2D systems. Additionally, this approach spontaneously results in the presence of polarized structures necessary for drug metabolism and improves functional longevity to over 75 days. Overall, this research reveals a method to shift the phenotype of existing IPSC-Heps towards primary adult hepatocytes allowing such cells to be a more relevant replacement for the current primary standard.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899231PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086372PLOS

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