Researchers at Wake Forest University Baptist Medical Center's Institute for Regenerative Medicine demonstrated the generation of a bioengineered human liver organoid using a liver bioscaffold made from an intact liver extracellular matrix, and filled (seeded) with primary human liver progenitor and endothelial cells.
The ability to generate a liver scaffold and preserve its vascular network had been demonstrated previously. These studies showed the possibility of seeding these bioscaffolds with liver cells from animals, but the possibility of generating functional human hepatic tissue was still in question.
The current study demonstrated that human liver cells can be seeded through the portal vein of the liver bioscaffold, and can be maintained in a specialized bioreactor with constant culture medium perfusion up to one week. Progressive human liver tissue formation was documented, as well as liver-associated functions. Widespread cell proliferation inside the bioengineered liver tissue with low cell apoptosis was also observed.
According to Pedro Baptista, PharmD, PhD, "These studies provide the basis to begin transplantation of bioengineered livers in small animal models. We believe that this functional hepatic tissue, once transplanted, will maintain and further gain function as it progressively grows and develops in vivo. Also, the exclusive use of human cells opens new horizons for drug testing and toxicology studies. This will more closely mimic drug metabolism in the human liver, which animal models can, at times, be extremely difficult to predict."
"This technology may provide a new approach for liver bioengineering, enabling the use of organ scaffolds with human cells to produce functional human liver tissue," said Dr. Baptista.
The researcher hails this as a new approach to whole organ liver bioengineering that might prove to be critical for drug discovery and treatment of liver disease. "This laboratory-generated hepatic tissue offers great potential as a drug discovery and toxicology testing platform. Moreover, we believe that further translation into larger animal species opens the door for the generation of transplantable bioengineered human livers that can help patients with end-stage chronic liver disease who are waiting for a donor."