HeadlinesBriefing favicon HeadlinesBriefing.com

Mini-livers: A New Hope for Liver Treatment

Financial Times Companies •
×

The trouble with a liver transplant is that you need a liver, an operating theatre and a patient fit enough to undergo the gruelling procedure. Each of those presents a challenge: the demand for organs outstrips supply; the specialised surgery is not widely affordable or available; and the sickest miss out, with between 5 and 10 per cent of UK patients dying on the waiting list. Scientists at the Massachusetts Institute of Technology are working on a fix: injectable “mini livers” that plug into the body’s blood supply and produce the same mix of proteins and enzymes that natural liver cells do.

The idea, so far tested only in mice, is that, in the absence of a replacement organ, these miniature tissue grafts could take on some of the life-saving functions of liver cells: helping with blood clotting, detoxifying the bloodstream and breaking down medicines. It offers a new twist on regenerative medicine — defunct organs being augmented by a constellation of smaller, specially engineered replacements. These satellite mini-organs — which, scientists say, can sit anywhere in the body that allows them to hook in and start working — could even one day supersede transplantation, which itself seemed a miracle when it was pioneered last century.

By chance, the first whole-organ transplant — the transfer of a kidney between two identical twins — took place in a Massachusetts hospital in 1954. The latest research is being led by Sangeeta Bhatia, a medic, engineer and MIT professor who is researching non-surgical ways of improving liver function. Simply injecting liver cells, called hepatocytes, into the body is not always effective; they often disperse (though the approach is used to correct some genetic liver disorders).

Securing the cells to a biomaterial “scaffold” can help to keep them in place — but that requires surgical implantation. The leap forward came from mixing clusters of human liver cells with hydrogel microspheres, which are gel beads that can behave as a liquid or solid under different conditions. The gloopy mixture can be injected through a syringe but can coalesce once inside the body.

This stability, the researchers reasoned, should allow the liver cells to connect to the blood supply and start functioning. To test the idea, Bhatia and colleague Vardhman Kumar injected a mixture of human liver cells, hydrogel microspheres and fibroblasts — cells that help tissue to knit together — into the belly fat of healthy, immune-suppressed mice, using ultrasound to guide the injections to the right place. As the team reported in the journal Cell Biomaterials earlier this year, these tiny satellite livers stayed viable and trackable for the eight-week duration of the study, churning out the expected proteins.

The authors write that their findings “raise the possibility that hepatocyte transplantation could be pursued without reliance on major surgical procedures”. The injectable grafts, they suggest, could also be used as a bridging treatment while patients wait for a transplant, with booster injections able to dial up the dose. Patricia Lalor, professor of experimental hepatology at the University of Birmingham, said there was an urgent need to expand treatments for patients awaiting liver transplants and welcomed injectable microspheres as “impressive” but added that it would not imminently replace transplantation: “The injected cells represented only about 5 per cent of the total volume of a mouse liver, and were made from a mixture of human hepatocytes and fibroblasts only . . . more development would be required to replace all of the different cell types found in an entire damaged liver.” Lalor also pointed out the difficulty of sourcing cells without falling back on precious donated livers, and that immune rejection remained a risk. In future, hepatocytes could be cultivated from a patient’s own stem cells.

The MIT researchers have not said when their “mini-livers” might reach the clinic for...