World's first 'human liver' created from stem cells

In a world first, Japanese scientists have grown human liver tissue from stem cells, paving way for alleviating the critical shortage of donor organs.
Takanori Takebe and Hideki Taniguchi at Yokohama City University showed the generation of vascularised and functional human liver from human induced pluripotent stem cells (hiPSCs) by transplantation of in vitro grown liver buds (rudimentary liver).
The study demonstrates a proof-of-concept that organ bud transplantation offers an alternative approach for treating organ failure by generating a 3D and vascularised organ.
During the early liver organogenesis, liver progenitor cells delaminate from the foregut endodermal sheet and form a three-dimensional liver bud (LB), a condensed tissue mass that is soon vascularised.

Such large-scale morphogenetic changes depend on the orchestration of signals between liver, mesenchymal and endothelial progenitors prior to blood perfusion.
"These observations led us to hypothesise that three-dimensional (3D) liver bud formation can be mimicked in vitro by culturing hepatic endoderm cells with endothelial and mesenchymal lineages," researchers said

"Here, we found that, although cells were plated on 2D conditions, hiPSC-derived liver progenitos organised into macroscopically visible 3D liver bud (hiPSC-LBs, or "rudimentary liver") by cultivating with human endothelial cells and human mesenchymal cells, presumably mimicking the above stated early developmental interactions," they said.
Surprisingly, researchers observed a formation of developing endothelial networks along with homogenously distributed hiPSC-liver progenitors even in vitro.

Immunostaining and gene expression analyses revealed resemblance between in vitro grown hiPSC-LBs and in vivo liver buds.
Transplantation of hiPSC-LBs resulted in a formation of functional human vasculatures by connecting to the host vessels just within 48 hours.
The formation of functional vasculatures stimulated the maturation of hiPSC-LBs into tissue resembling the adult liver with multiple liver-specific functions such as protein production and human-specific drug metabolism.
Furthermore, mesenteric transplantation of hiPSC-LBs rescued the drug-induced lethal liver failure model.
"Thus, to our knowledge, we firstly demonstrated that the generation of functional human organ from pluripotent stem cells," researchers said.
"Our study demonstrates a proof-of-concept that "organ bud transplantation" offers an alternative approach resulting in the generation of a 3D, vascularised organ.

"These results highlight the enormous therapeutic potential using in vitro grown organ bud transplantation for treating organ failure," researchers said.
The study was published in the journal Nature.