Scientists look to grow 'mini livers' for patients with organ damage
15 November, 2022
It sounds like science fiction: people with end-stage liver disease are injected with cells from a donor liver and, in response, their body produces multiple mini livers that keep them healthy.
Yet, science fiction really could be on the verge of becoming scientific fact, because US company LyGenesis is about to begin clinical trials in which participants are expected to develop such “ectopic” livers.
What is more, LyGenesis’s method could see as many as 75 patients receive liver cells from a single donated organ, and organs that have been discarded from transplant programmes are likely to be suitable for the technique.
It represents a stark contrast to standard transplant surgery, where just a single patient benefits for each donated organ, and that organ must have passed quality checks.
After decades of overblown expectations and false starts for regenerative medicine, where old or non-functioning organs or tissues are replaced, it represents a potentially significant development.
“In the US, 30 to 40 per cent of livers are donated but discarded. So there is this robust cell source. We can access that cell source and use it as the starting point to develop our cell therapy,” said Michael Hufford, the chief executive and co-founder of LyGenesis, which was founded in 2017 and is based in Pittsburgh, Pennsylvania. Among all the body’s organs, the liver is particularly suitable for this type of treatment because, as Mr Hufford puts it, it is “the only organ in our bodies that naturally tries to regenerate”.
Indeed, even with end-stage liver disease, he said the liver is trying to regenerate and is emitting multiple biochemical growth signals.
But issues such as fibrosis — thickening or scarring — have made the organ such an inhospitable environment that the hepatocytes — the liver cells — cannot thrive.
“So when we grow these ectopic organs, they continue to receive the pro-growth signals from the diseased organ. Those pro-growth signals we expect will sustain those ectopic organs,” Mr Hufford said.
“As long as the patient continues on immune suppression, we expect those ectopic organs to continue to provide therapeutic benefits to the patients.”
The idea for the ambitious technique comes from LyGenesis’s chief scientific officer, Dr Eric Lagasse, an associate professor at the University of Pittsburgh.
How will the body grow healthy cells?
More than a decade ago, he found that in mice with a genetic flaw that caused them to have a fatal liver disease, when hepatocytes, the most common cells of the liver, were injected into them, the cells would make their way to the lymph nodes — swellings in the lymphatic system — and form liver tissue.
The technique has subsequently been tested on a variety of other mammals and now LyGenesis is enrolling patients for the first clinical trial, set to begin at Massachusetts General Hospital in the coming months.
The clinical trials will start with four patients, each of whom will have about 50 million hepatocytes — the human liver has more than 100 million hepatocytes per gram of tissue — injected into a single lymph node.
An endoscope will go down through the mouth and, using a camera and ultrasound, a lymph node is identified, and a needle will inject the liver cells. The whole procedure is likely to take as little as 10 minutes.
The cells are likely to multiply many times over and form a functioning mini organ, an ectopic — meaning in an abnormal place — liver.
Patients will be carefully monitored and, if all goes well, months later a second group will have cells injected into three lymph nodes. Later, a third group will have them injected into five lymph nodes.
“The cost of goods for our therapy is remarkably low relative to other cell therapies,” Mr Hufford said. “Part of the reason for that is the origination of the cells are these donated but otherwise discarded organs.”
It takes three people about six hours in the lab to process a liver and prepare enough samples for dozens of patients.
The whole clinical trial is likely to take about two years and Mr Hufford, who has lengthy experience in clinical trials, acknowledges that there are likely to be “unanticipated challenges”.
Further clinical trials will be needed and, if the timetable does not have to be stretched out, approval from the US Food and Drug Administration could happen from 2027 onwards.
Mr Hufford said the technique will not remove the need for complete liver transplants in all patients who are treated.
In such patients it may act as a “bridge to transplant”, keeping the individual healthy until a donor organ becomes available.
“For some patients, we hope to provide a curative effect, for others it may be that what we’re really providing is time, and time for a full organ transplant to become available,” Mr Hufford said.
While the liver, which is known for its ability to regenerate, is the key focus of the work, a similar approach could also be used with the kidneys, pancreatic islets, which make hormones including insulin, and the thymus, a small gland involved in the immune system.
As with individuals who receive an organ transplant, patients injected with liver cells will have to take drugs to suppress their immune system to prevent it from targeting the “foreign” hepatocytes.
LyGenesis is collaborating with another biotechnology company, iTolerance, which works on ways to reduce this immune rejection.
Jacqueline Jeha, LyGenesis’s director of clinical operations and corporate development, said the growing of ectopic organs potentially offers a “remarkable” opportunity to improve patients’ quality of life.
“It certainly is a solution to an unmet need for patients who would be sitting waiting for an organ transplant for, sometimes, until death. We’re giving patients an opportunity for longevity,” she said.
Future of regenerative medicine
The field of regenerative medicine, which aims to replace failing tissues and organs, has been the focus of research for decades.
Indeed, said Prof Alvaro Mata, professor in biomedical engineering and biomaterials at the University of Nottingham in the UK, there have been attempts “to repair and regenerate tissues for thousands of years”. He cites artificial eyes made from mud and wood produced in Ancient Egypt.
In modern times, it has often been found, he said, that progress has been “more difficult than people initially thought”.
Efforts from two or three decades ago for example, to generate tissues in the laboratory that could subsequently be implanted into patients often foundered.
“The companies that started went bankrupt because it was just too difficult and it was just too expensive,” Prof Mata said.
“We became humbled by how incredible our bodies are. There are so many things we don’t understand — biological processes.”
More successful, he said, have been approaches that work with biology and that “let cells do what they want to do without completely understanding what is happening”.
“It’s a recognition of the complexity of biology and a recognition that we may not be able to recreate everything, but perhaps we can steer things in a more hands-off manner,” he said.
Now, with new approaches being pioneered and “after in some ways decades of false starts”, it is “a remarkable time to be working in regenerative medicine”, said Mr Hufford.
“As a field in general, regenerative medicine finds itself in the launch pad,” he said.
“The ability to grow an ectopic organ that can exert a life-saving effect for a patient, that really was the stuff of science fiction just a few years ago.
“We’re witnessing a dramatic acceleration in the development of novel bio-therapeutics."
Source: www.thenationalnews.com
TAG(s):