Successful Mass Production of Bioengineered Liver Tissue using New Technique

Bioengineered Liver Tissue

The technique could provide viable and consistently produced liver transplants, which can effectively treat patients with liver disease.

Researchers at Yokohama City University and Cincinnati Children’s Center for Stem Cell and Organoid Medicine on December 11, 2017, revealed that they have developed a large-scale method for production of bioengineered liver tissue from human induced pluripotent stem cells (iPSCs).

Including animal cell in same environment to develop the human cells and growing human cells or tissues for organ replacement to create enough tissue are the major limitation faced by researchers. Animal cells produce substances that could cause negative effects in patients, such as immune rejection. According to Organ Transplant Market Report published by Coherent Market Insights, increasing number of patients awaiting for organ transplant and increase in mortality rate due to the inadequate organ for transplantation might create opportunities for mass production of bioengineered liver tissue, which can be used for liver transplant.

Researchers have developed a system that could overcome these limitations with allowing the mass production of liver organoids without the use of animal products. This new technique creates batches of 20,000 liver micro-buds at once that could be combined to achieve a size and number of liver cells that is sufficient for one transplant. The organoids are composed entirely of human iPSCs to avoid graft rejection. Liver tissues were generated in U-shaped bottom micro-well cell plates. The plates are custom-designed and they contain a film layer inside the micro-wells to help the liver buds to grow and thrive.

Using iPSCs from human donors, three types of liver progenitor cells were grown, which was required to generate healthy livers. The progenitor cells formed into three-dimensional liver buds by communicating with each other and self-organizing. The team was able to grow 20,000 liver buds per well, which were enough for therapeutic transplants. Liver buds were tested in mouse models with liver disease and the transplants successfully rescued the mice from liver disease.

“Because we can now overcome these obstacles to generate highly functional, three-dimensional liver buds, our production process comes very close to complying with clinical-grade standards,” said Takanori Takebe, a researcher involved in the study. “The ability to do this will eventually allow us to help many people with final-stage liver disease. We want to save the lives of children who need liver transplants by overcoming the shortage of donor livers available for this.”

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