Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering

Wei Cheng Jiang, Yu Hao Cheng, Meng Hua Yen, Yin Chang, Vincent W. Yang, Oscar K. Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture invitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation invivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs.

Original languageEnglish
Pages (from-to)3607-3617
Number of pages11
JournalBiomaterials
Volume35
Issue number11
DOIs
StatePublished - Apr 2014

Keywords

  • Acellular liver scaffolds
  • Hepatic-like tissues
  • Mesenchymal stem cells
  • Transplantation

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