4.6 Review

Hepatocyte-like cells derived from induced pluripotent stem cells

Journal

HEPATOLOGY INTERNATIONAL
Volume 11, Issue 1, Pages 54-69

Publisher

SPRINGER
DOI: 10.1007/s12072-016-9757-y

Keywords

iPS cells; Reprogramming; Hepatocyte-like cells; Directed differentiation; Cellular models of disease; Cell transplantation

Funding

  1. New York Stem Cell Foundation [CO26440, R01 DK064670, R33 CA121051]
  2. [1PO1 DK 096990-01]
  3. [RO1 DK092469]
  4. [P30 DK041296-28]
  5. [R01 DK100490-01A1]

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The discovery that coordinated expression of a limited number of genes can reprogram differentiated somatic cells to induced pluripotent stem cells (iPSC) has opened novel possibilities for developing cell-based models of diseases and regenerative medicine utilizing cell reprogramming or cell transplantation. Directed differentiation of iPSCs can potentially generate differentiated cells belonging to any germ layer, including cells with hepatocyte-like morphology and function. Such cells, termed iHeps, can be derived by sequential cell signaling using available information on embryological development or by forced expression of hepatocyte-enriched transcription factors. In addition to the translational aspects of iHeps, the experimental findings have provided insights into the mechanisms of cell plasticity that permit one cell type to transition to another. However, iHeps generated by current methods do not fully exhibit all characteristics of mature hepatocytes, highlighting the need for additional research in this area. Here we summarize the current approaches and achievements in this field and discuss some existing hurdles and emerging approaches for improving iPSC differentiation, as well as maintaining such cells in culture for increasing their utility in disease modeling and drug development.

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