A team of researchers has developed "mini-pathways" to save children suffering from acute liver failure by avoiding liver transplantation.
Massimiliano Paganelli , pediatric hepatologist and Director of the Tissue Engineering and Hepatic Cell Therapy Laboratory at CHU Sainte-Justine, is well acquainted with the reality of young people and adults suffering from liver failure, as he regularly sees them in clinic. This health problem often requires a liver transplant to be performed as quickly as possible. The challenges associated with this type of medical situation, such as the scarcity of available organs, led him down the path of discovery.
Together with Claudia Raggi and her team at CHU Sainte-Justine and Université de Montréal, Paganelli has succeeded in developing mature liver tissue from stem cells. With the appearance of patches measuring around 10 centimetres on a side, this encapsulated liver tissue, composed of "minifoils" and innovative biomaterials, can be produced in advance so as to be available as soon as a need arises.
The device is then implanted laparoscopically, a minimally invasive procedure lasting just 10 minutes. And the preliminary results are astounding: "From the moment we produce it, the device is as functional as a mature liver," enthuses the doctor, who is also a professor at the Université de Montréal Faculty of Medicine. So, two hours after being implanted, it is already taking over from the diseased organ. And because the cells are isolated within the device, they never come into contact with the patient’s immune system. This eliminates the need for immunosuppressive drugs, which are required for transplants, and reduces the risk of complications."
A very dangerous situation for the child’s life
Acute hepatic failure (AHF) is a serious failure of the liver, often caused by a virus or the inappropriate use of a drug. Because it prevents the organ from eliminating toxins from the body, AHI often requires a liver transplant to be performed very quickly. And while liver transplantation can save lives, it is a procedure with its own risks and consequences.
"In cases of acute liver failure, we only have a few days to perform a liver transplant, but finding a compatible organ in a very short time is often a major challenge, especially when the disease strikes young children," says Massimiliano Paganelli. I remember a young Canadian girl who suffered from HAI in Saudi Arabia. As the disease was too severe to allow her to return to Montreal, the teenager was evacuated to Europe, where she quickly underwent a liver transplant thanks to a portion of her father’s liver."
Liver transplantation and its complications
The girl in question survived the transplant and was subsequently taken to CHU Sainte-Justine, where she was cared for by Mr. Paganelli. After years, she is doing well, but is dependent on ongoing treatment and must undergo periodic check-ups.
"You have to consider that transplantation is a complex surgery, with still a high mortality rate, fairly serious short- and long-term complications and lifelong intake of immunosuppressive drugs," explains the hepatologist. This is frustrating in the case of HIA, because the liver has an excellent capacity for regeneration, which would enable it to heal on its own - if only we were able to keep the person alive for the time required."
Faced with these difficulties, Mr Paganelli wanted to find a solution that was both more effective and less invasive. And that solution was cell therapy.
The technology we developed at CHU Sainte-Justine was extremely promising," says the physician-researcher. However, for such an innovation to eventually become available to patients, we had to prove that the processes were safe and optimal. We therefore founded Morphocell Technologies in 2018 to be able to develop the technology and processes needed to produce and carry out tests on a larger scale. Our goal has always been to help our patients and save lives."
Today, this cell therapy called ReLiver is proving its worth. Clinical trials have shown that it accelerates liver regeneration. Once this process is complete, the "patch" is simply removed and the liver healed. "Eventually, I’m confident that we’ll be able to avoid up to 80% of liver transplants in our HAI patients," enthuses the doctor.
Innovating for the benefit of patients: promising clinical trials
"In the end, we managed to save this young girl who had been rushed to hospital in Europe. But I tell myself that, if our technology had been available at the time, we could have intervened more quickly and with less risk, without her even having to leave Saudi Arabia, where she could have been treated and continued her life with her own liver", mentions Massimiliano Paganelli.
The technology is currently in the pre-clinical stage and therefore cannot yet be offered to patients. Nevertheless, the latest news is cause for celebration: the company today announced a major new $50 million financing from private funds. This investment will enable the company to complete preclinical development and carry out the first clinical trial, confirming the safety of the process and the possibility of future international implementation. A clinical trial on adults with HAI is due to start in 2026, and Mr Paganelli hopes to have patients benefiting from the treatment the following year. If the trials are conclusive, the hepatologist’s wish is for this innovation to benefit children as soon as possible.
For Anne-Marie Alarco, Assistant Director of Innovation at CHU Sainte-Justine, this success demonstrates the hospital’s immense potential for innovation in healthcare: "Dr Paganelli has made a bold bet to change things. Drawing on his experience as a researcher and clinician, through Morphocell Technologies he is brilliantly bringing to fruition a transformative innovation for our little patients." In the longer term, the ambition is to explore the potential of this innovation to treat other liver conditions, particularly chronic diseases, and even to treat other organs.
