The scientists of the Indian Institute of Technology Kanpur (IIT-K) have developed Bio-Artificial Liver (BAL) as an extracorporeal device which can be used for treating patients with acute-on-chronic liver failure (ACL) where liver transplantation still remains the gold standard treatment.
This research development has been carried out in association with the Institute of Liver and Biliary Sciences (ILBS), Delhi and has been supported by the Department of Biotechnology (DBT), Ministry of Science and Technology, Govt. of India. This research was also supported by the International scientists from Japan under Indo-Japan collaboration supported by Department of Science and Technology (DST), Govt. of India and Japan Society for the promotion of science (JSPS).
IIT-K filed the patent for BAL device both at the National and at the International level. The work was also published in “Scientific Reports” of Nature publishing group.
A senior professor in the Department of Biological Sciences and Bioengineering (BSBE) at IIT Kanpur, Professor Ashok Kumar said that an integrated BAL device had been developed for the first time by his team. The device is unique by its design and functionality as it integrates both the functions of an artificial liver and bio-artificial liver in a single device.
The BAL device has been tested on animal liver failure models and has shown encouraging results. The device has also been tested offline on the plasma of the acute-on-chronic liver failure patients which has shown promise of its application for human beings. The device will be connected to patients externally as a dialysis unit.
The scientists at the BSBE said that the work on developing the bio-artificial liver was being carried out in many countries of the world for the past several years. Different models of the bio-artificial liver system were developed, but the present device developed at IIT Kanpur has integrated features of artificial and bioartificial liver functions in an elegantly compact design which makes it more versatile in function and is more likely to succeed in clinical applications with patients.
“The artificial liver devices are being used in clinics successfully for liver detoxification, but bio-artificial liver which will provide synthesis and metabolic functions has yet to come in real clinical use. Thus, IIT-K extracorporeal BAL device may provide hope for patients in the future for detoxification, synthesis, and metabolism which are essential functions of the healthy liver. This BAL device is superior to any other bio-artificial liver devices as the liver cells in this device are sustained for longer period of time and can provide proper synthesis and metabolic functions, whereas unique membrane used in the device provides detoxification of harmful toxins in the liver and thus performs dialysis function as well in the patient’s plasma’, said Professor Ashok Kumar.
“Before connecting the BAL device externally to the body, the liver cells are proliferated in the BAL device. During animal tests, it was connected into rodent models where 70% of the liver was excised, or acute liver injury was created by toxic substances like CCL4 (carbon tetrachloride), and in more than ninety percent cases the damaged liver of the animals was recovered in 2-3 hours of treatment. The recovered animals restored more than seventy percent of normal functioning.”
To bring the integrated device to life in real-time situations, Prof. Kumar’s team will now be upscaling the design for stage II pre-clinical trials in higher animal models (Rabbit and Pig). The major focus of the studies would be to increase the survival time of the diseased so as to buy time for liver regeneration or transplantation. The strategy behind would be to improve the efficiency of detoxification unit to circumvent the abrupt rise in toxicity levels of blood plasma. Subsequently, this will enhance the lifespan of extracorporeal liver cells resulting in an optimum amount of protein synthesis and metabolism.
The BAL would be a boon for the Liver failure patients. It could be used in the patient till the original liver which was damaged could be recovered. In case the liver was completely damaged, the patient can get a lease of life with the help of BAL till the liver becomes available for transplantation.
Figure: Integrated hybrid cryogel-based bioreactor design. (A) Dimensions of the bioreactor; (B) Constituents of the three compartments; (c) Compact bioreactor design with chambers clubbed together.