Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.
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 in vitro. 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 in vivo. 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.
Institute of Biomedical Engineering, National Yang-Ming University, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taiwan. Electronic address: windszzz@gmail.com.
Wei-Cheng
WC
Jiang
Faculty of Medicine, National Yang-Ming University, Taiwan. Electronic address: ray800201@yahoo.com.tw.
Yu-Hao
YH
Cheng
Stem Cell Research Center, National Yang-Ming University, Taiwan. Electronic address: emh1989@gmail.com.
Meng-Hua
MH
Yen
Institute of Biomedical Engineering, National Yang-Ming University, Taiwan. Electronic address: yichang@ym.edu.tw.
Yin
Y
Chang
Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY, USA. Electronic address: vyang@sbumed.org.
Vincent W
VW
Yang
Department of Medical Research & Education, Taipei Veterans General Hospital, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taiwan. Electronic address: kslee@vghtpe.gov.tw.
Oscar K
OK
Lee
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D003080:Cold Temperature; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D016031:Liver Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D015415:Biomarkers
Acellular liver scaffolds; Hepatic-like tissues; Mesenchymal stem cells; Transplantation