this is one of the most exciting stories of the past few days. Although it is not close to clinical applications yet, it represents a tremendous research direction. The most fascinating element of it to me is how the body knows how to build a liver. We just need to learn to harness the wisdom that is already in the body…
To grow a liver, researchers led by MIT engineer Sangeeta Bhatia started by carefully designing a cellular scaffold for the organ to grow on. They first got human liver cells (hepatocytes) and connective tissue cells (fibroblasts) to grow together in clumps. Then they used a micro-tissue molding to create ropes endothelial cells, which make up the lining of blood and lymphatic vessels. Last, they carefully assembled rows of the cell clumps in between strands of endothelial chords and held the structure together with a biodegradable hydrogel.
In all, they called the organ starter kit SEED, for “In Situ Expansion of Engineered Devices.”
To test out the SEEDs, the researchers implanted them into the belly fat of healthy mice and mice with a genetic disorder that causes liver damage. In the healthy mice, the liver seeds didn’t grow very much. But in the rodents with liver damage—which were circulating liver-regenerating growth factors and other molecular signals to repair their damaged liver—the organ SEEDs sprouted.
Eighty days after implantation, there was a 50-fold cellular expansion along the SEED’s scaffold. The liver organoid formed precursor bile ducts and contained clusters of red blood cells, suggesting vasculature formation. The organoid also pumped out standard human liver proteins, including albumin and transferrin.
There’s a lot more work to go before researchers have a human-sized, functional liver, but the team is optimistic. “We believe that this work sets the stage for using SEEDs as an alternative strategy for scale-up of engineered organs, one that uses native developmental, injury, or regenerative signals to expand prefabricated constructs in situ,” they conclude.