Startup wants to regrow livers in humans, and it could transform organ donation

LyGenesis and iTolerance seem ready to save people with devastating liver diseases who are not eligible for transplants.

In the coming weeks, a volunteer in Boston, Massachusetts, will be the first to trial a new treatment that could end up creating a second liver in their body, according to MIT Technology Review published on Thursday.

LyGenesis' lead development asset is a liver regeneration study documented in Liver Transportation — was carried out by Paulo Fontes et al.

The company's goal is to inject liver cells from a donor into the lymph nodes of sick recipients. This can lead to the protrusion of miniature organs in the body. These mini-livers are thought to compensate for useless ones.

The study was successful when tested in mice and pigs. Time will tell whether it will affect humans or not.

"In this study, a human liver disease (tyrosinemia Type I) was modeled in swine, and liver cells transplanted into lymph nodes were capable of forming ectopic livers that cured all of the animals of otherwise fatal liver disease. The engraftments were again shown to be safe and also structurally and functionally similar to native liver tissue," explained LyGenesis in its statement.

Ectopic organs for everyone

"The development and FDA approval of novel therapies for life-threatening diseases requires a rigorous approach to preclinical studies, and our ability to grow ectopic organs to support failing organs in patients is no exception," said Dr. Paulo Fontes, LyGenesis's Chief Medical Officer and former Director of the Liver Transplant Program, Starzl Transplant Institute at the University of Pittsburgh Medical Center.

"Showing that our cellular therapy was able to safely and effectively induce organogenesis – the forming of a novel, a well-vascularized organ within the body – in multiple models of liver disease in large animals was a crucial step toward beginning our forthcoming clinical trial for patients with end-stage liver disease who are currently ineligible for standard liver transplantation."

It will be revolutionary

If successful in humans, the study will be revolutionary for both the scientific community and patients, says MIT. The new approach can make use of organs that would otherwise have been discarded, and the researchers reckon they can get treatments for around 75 people from a single donated organ.

“It’s very promising,” says Valerie Gouon-Evans, a stem-cell biologist with a focus on liver regeneration, who is not involved in the research or with the company. “I’m really happy … this idea is getting into the clinic.”

Transplant is not the only way

As MIT reported, Eric Lagasse from LyGenesis — who is a stem-cell biologist at the University of Pittsburgh, has spent years researching cell-based treatments for liver disease. He said transplant doesn't work especially well for patients who are not well, and it's not the only solution.

Around 10 years ago, he was experimenting with the idea of injecting cells from healthy livers into diseased ones in mice. Only a small number of mice survived.

When Lagasse and his colleagues later performed autopsies on those survivors, “I was very surprised,” he recalled. “We had a mini liver present … where the lymph node would be," he said.

Study abstract

Orthotopic liver transplantation continues to be the only effective therapy for patients with end-stage liver disease. Unfortunately, many of these patients are not considered transplant candidates, lacking effective therapeutic options that would address both the irreversible progression of their hepatic failure and the control of their portal hypertension. In this prospective study, a swine model was exploited to induce subacute liver failure. Autologous hepatocytes, isolated from the left hepatic lobe, were transplanted into the mesenteric lymph nodes (LNs) by direct cell injection. At 30-60 days after transplantation, hepatocyte engraftment in LNs was successfully identified in all transplanted animals with the degree of an ectopic liver mass detected being proportional to the induced native liver injury. These ectopic livers developed within the LNs showed remarkable histologic features of swine hepatic lobules, including the formation of sinusoids and bile ducts. On the basis of our previous tyrosinemic mouse model and the present pig models of induced subacute liver failure, the generation of auxiliary liver tissue using the LNs as hepatocyte engraftment sites represents a potential therapeutic approach to supplement declining hepatic function in the treatment of liver disease.