Lab-Grown Liver and Gut Tissue Without Tumors

Researchers from Cincinnati Children’s Hospital and Yokohama City University in Japan led by NYSCF — Robertson Stem Cell Investigator Takanori Takebe, MD, have developed a technique for producing human liver and gut tissue that stays tumor-free and is large enough for transplantation.

The study, published in Stem Cell Reports, outlines how the researchers transformed human induced pluripotent stem cells (iPSCs) into posterior gut endodermal progenitor cells (PGECs) by manipulating select genes and mimicking an embryonic environment. PGECs are naturally primed to become gastrointestinal tract cells, but haven’t yet been assigned to become stomach, liver, or intestinal cells. The researchers then programmed the PGECs to become hindgut and liver cells.

The advantage of using PGECs to make tissues is that they don’t form tumors. Often, gastrointestinal organoids or liver cells generated directly from iPSCs can form teratomas (benign tumors) because of genetic variation or chromosome instability. The organoids in this study, however, stayed healthy and stable (no tumors!) when transplanted into mice with liver disease and were able to successfully prevent liver failure.

One drawback to using progenitor cells to create organoids is that the process usually requires the use of animal byproducts, which aren’t safe for human transplantation. In this study, however, cells were engineered without animal byproducts, increasing the likelihood that they will one day be used for human transplant.

Another problem with growing human tissues is that they often aren’t big enough to be viable for transplantation and may not be functional in the body. But the tissues from this study were large enough to transplant into mice and were able to perform the liver’s primary function: filtering toxins. The cells also carried a significant propensity for multiplying in culture, growing by a factor of 10²¹ after being re-plated 20 times. This shows promise for their use in growing tissues large enough for transplantation into humans.

For more information about this study, check out the press release.