Researchers in Hyderabad claim to have developed a promising technology for creating in the lab “implantable bioengineered humanized” livers for the management of acute liver failure (ALF), one of the most devastating fatal conditions.
The technology, successfully demonstrated in animal experiments, “has enormous potential for clinical translation” in managing ALF patients desperately waiting for liver transplants, it is claimed.
The study by researchers at the Centre for Liver Research of the Deccan College of Medical Sciences (DCMS) has been reported in the Elsevier journal “Material Science & Engineering-C”. Currently liver transplantation has been the only treatment option available for ALF. But its wider applicability has been limited by high cost, non-availability of quality donor organs and the need to use immunosuppressive drugs throughout life.
It is here that the animal study by researchers at DCMS’s Centre for Liver Research raises hopes of an alternative approach although clinical trials in humans are yet to validate this. In their animal experiment, the DCMS researchers chemically-induced ALF in mice and then used their technology to make the affected livers functional again.
The experimental procedure involved harvesting the complete livers of the ALF mice with intact blood vessels (hepatic artery and portal vein) followed by decellularisation — a process that removes the intracellular components from the liver tissue while preserving only the liver “scaffold” and its native 3-dimensional architecture.
In the next step, the scaffold is “repopulated” with human hepatic progenitor cells that differentiate into “hepatocytes,” which constitute 80 per cent of the human liver. Finally, the laboratory-made, bioengineered humanised livers — in which mouse liver tissue has been replaced by human cells — are transplanted back into rats.
According to the DCMS researchers, the strategy for rapid and efficient decellularisation and repopulation adopted by them “is superior” to earlier approaches reported by other workers.
“Over the next years, we aim to optimise the technique in a larger scale to generate ready-to-use bioengineered humanised livers for supplying on demand and validate its safety and efficacy in human,” said report co-author Aleem Ahmed Khan. “Immediate human trials are desirable to benefit healthcare without further delay.”
Chaturvedula Tripura, a cell biologist at the CSIR-Centre for Cellular and Molecular Biology in Hyderabad said the DCMS study has demonstrated “an efficient and promising technology” for addressing ALF through bio-engineering and transplantation of humanised livers.
“The study is excellent scientific work,” added Sanjay Nagral, director of Surgical Gastroenterology at Jaslok Hospital & Research Centre in Mumbai. “The promise that the bio-engineered liver tissue, especially from other species holds for future human use is indeed interesting,” he said.
However, further studies are warranted to explore the suitability of this strategy in larger animal models and future human trials, the researchers say.