Human Liver Organoids Thrive When Transplanted into Mouse Liver Failure Model

Liver disease researchers have demonstrated in a mouse model that it may be feasible to treat some types of liver failure with transplanted multicellular liver organoid units composed of a heterogeneous cellular population that includes adult stem and progenitor cells.

Liver disease affects large numbers of patients, yet there are limited treatments available to replace absent or ineffective cellular function of this crucial organ. The only effective therapy for end-stage liver failure is liver transplantation, which is profoundly limited by scarce donor supply and the necessity for life-long immunosuppression treatment. On the other hand, in some conditions, such as inborn errors of metabolism or transient states of liver insufficiency, patients may be treated by providing partial quantities of functional liver tissue.

In order to develop a robust means for transplanting functional donor liver tissue, investigators at The Saban Research Institute of Children's Hospital Los Angeles (CA, USA) transplanted multicellular human or mouse liver organoid units composed of a heterogeneous cellular population that included adult stem and progenitor cells into a mouse model of inducible liver failure.

They reported in the August 30, 2016, online edition of the journal Stem Cells Translational Medicine that both mouse and human tissue-engineered liver (TELi) formed in the animals. TELi contained normal liver components such as hepatocytes with albumin expression, CK19-expressing bile ducts and vascular structures with alpha-smooth muscle actin expression, desmin-expressing stellate cells, and CD31-expressing endothelial cells. After four weeks, TELi contained proliferating albumin-expressing cells, and identification of beta-2-microglobulin-expressing cells demonstrated that the majority of human TELi in the mice was composed of transplanted human cells. Human albumin was detected in the host mouse serum, indicating the development of in vivo secretory function.

"Based on the success in my lab generating tissue-engineered intestine and other cell types, we hypothesized that by modifying the protocol used to generate intestine, we would be able to develop liver organoid units that could generate functional tissue-engineered liver when transplanted," said senior author Dr. Tracy C. Grikscheit, professor of surgery at The Saban Research Institute of Children's Hospital Los Angeles.

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The Saban Research Institute of Children's Hospital Los Angeles