Current status of hepatocyte-like cell therapy from stem cells

Surg Today. 2021 Mar;51(3):340-349. doi: 10.1007/s00595-020-02092-6. Epub 2020 Aug 4.

Abstract

Organ liver transplantation and hepatocyte transplantation are not performed to their full potential because of donor shortage, which could be resolved by identifying new donor sources for the development of hepatocyte-like cells (HLCs). HLCs have been differentiated from some stem cell sources as alternative primary hepatocytes throughout the world; however, the currently available techniques cannot differentiate HLCs to the level of normal adult primary hepatocytes. The outstanding questions are as follows: which stem cells are the best cell sources? which protocol is the best way to differentiate them into HLCs? what is the definition of differentiated HLCs? how can we enforce the function of HLCs? what is the difference between HLCs and primary hepatocytes? what are the problems with HLC transplantation? This review summarizes the current status of HLCs, focusing on stem cell sources, the differentiation protocol for HLCs, the general characterization of HLCs, the generation of more functional HLCs, comparison with primary hepatocytes, and HLCs in cell-transplantation-based liver regeneration.

Keywords: Cell transplantation; Differentiation; Hepatocyte-like cells; Stem cells.

Publication types

  • Review

MeSH terms

  • Bone Morphogenetic Proteins / physiology
  • Cell Differentiation* / genetics
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Coculture Techniques
  • Cytological Techniques / methods*
  • Fibroblast Growth Factors / physiology
  • Hepatocyte Nuclear Factor 4 / physiology
  • Hepatocytes / transplantation*
  • Homeodomain Proteins / physiology
  • Humans
  • Liver Diseases / therapy*
  • Liver Regeneration / physiology
  • SOXF Transcription Factors / physiology
  • Stem Cells / physiology*
  • Transcription Factors / physiology

Substances

  • Bone Morphogenetic Proteins
  • HHEX protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Homeodomain Proteins
  • SOX17 protein, human
  • SOXF Transcription Factors
  • Transcription Factors
  • Fibroblast Growth Factors