Researchers at Yokohama City University and Cincinnati Children’s Center for Stem Cell and Organoid Medicine have developed a large-scale method to produce bioengineered liver tissue from human induced pluripotent stem cells (iPSCs). The technique could provide viable, consistently produced liver transplants, offering hope to patients with liver disease.
One of the limitations faced by scientists trying to grow certain human cells in the lab for therapeutic purposes is the need to include animal cells in the same environment to help the human cells grow. Such animal cells produce substances that could cause negative effects in patients, such as immune rejection, making human cells grown under these conditions potentially unsuitable for therapeutic applications.
Another challenge in growing human cells or tissues for organ replacement is scaling the process to create enough tissue. In a recent study, the researchers reported that they have developed a system that could overcome these obstacles, and allows the mass production of liver organoids without the use of animal products.
The team’s new technique involves creating batches of up to 20,000 liver micro-buds that could be combined to achieve a size and number of liver cells that is sufficient for transplant. The organoids are composed entirely of human iPSCs and so avoid any difficulties associated with animal products.
The research team generated the liver tissues in U-shaped bottom micro-well cell plates. The plates, which are custom-designed, contain a film layer inside the micro-wells to help the liver buds to grow and thrive. The team used chemical approaches to design this film layer, meaning that animal cells are not needed in the wells.
Using iPSCs from human donors, the researchers grew three types of liver progenitor cells required to generate healthy livers. The progenitor cells formed into three-dimensional liver buds by communicating with each other and self-organizing. The team could grow a whopping 20,000 liver buds per well, meaning that the technique could produce enough cells for therapeutic transplants. The team tested the liver buds in mouse models of liver disease, and the transplants 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,” commented 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.”
See the following video for an overview of the organoid research conducted by the Cincinnati Children’s Center for Stem Cell and Organoid Medicine: