Background. Liver transplantation remains the only viable therapy for liver failure but
has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D
bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate
the role of Wnt/ -catenin signaling in liver development and generation. Methods. Dissected
rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and
Cells 2021, 10, 2819. https://doi.org/10.3390/cells10112819 https://www.mdpi.com/journal/cells
Cells 2021, 10, 2819 2 of 25
III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion
procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA
content. Liver recellularization was assessed through histological examination and measurement of
transcript levels of Wnt/ -catenin pathway, hepatogenesis, liver-specific microRNAs and growth
factors essential for liver development. Adult rat liver decellularization was confirmed by the
maintenance of ECM proteins and persistence of growth factors essential for liver regeneration.
Results. iPSCs seeded rat decellularized livers displayed upregulated transcript expression of
Wnt/ -catenin pathway-related, growth factors, and liver specification genes. Further, recellularized
livers displayed restored liver-specific functions including albumin secretion and urea synthesis.
Conclusion. This establishes proof-of-principle for the generation of three-dimensional liver organ
scaffolds as grafts and functional re-establishment. |
