Autumn flowers are in full bloom at Jakkur in Bengaluru. The leafy campus of the National Centre for Biological Sciences on Bellary Road is a haven for birdlife. Almost every tree on the campus has a nest.
Life sprouts inside the laboratories, too. The three-dimensional tissues developed by researchers of Pandorum Technologies, a biotechnology startup on the campus, can mimic the human liver.
The tissues are exactly like the human liver tissues when you see them under the microscope. Better, they can perform the functions of a human liver—produce important proteins, store glycogen and clear metabolic waste. They can stay alive only in a temperature-controlled lab environment and are stable for up to four weeks.
What excites Arun Chandru, director and cofounder of Pandorum, the most is that these tissues can enable medical research with fewer animal and human trials. “You can even develop diseased models with these tissues. For instance, liver stage malaria or viral hepatitis can be studied by infecting our liver tissues with the parasite or virus. They are particularly useful for research on neglected and rare diseases,’’ he says.
They can be of great help to medical researchers when a quick response is required to combat an epidemic. The manufacturing of these tissues can be scaled up as per requirement, which is not possible with animal or human models.
The tissues can be a valuable tool in the development of new drugs and vaccines as well. “They would be useful in drug screening, substantially decreasing the use of whole animals to test toxicity and metabolism of new drugs,” says Prof G. Padmanaban, former director, Indian Institute of Sciences, who is also a senior science and innovation adviser at the Biotechnology Industry Research Assistance Council, of the department of biotechnology.
Pharmaceutical companies spend crores of rupees and many years on medical research and drug development. The 3D printed tissues can make it faster and safer at a significantly reduced cost. French cosmetic giant L’Oreal last year partnered with Organovo, a bioengineering startup, to make 3D printed human skin to test its cosmetics. Other cosmetic companies are also looking for alternatives for cosmetic testing. The researchers at Pandorum see their artificial liver tissues useful on such test platforms.
Pandorum Technologies has a multi-disciplinary team consisting of people with expertise in stem cell biology to aerospace engineering. “The process, in its present form, involves bioprinting of a three-dimensional tissue architecture with different liver cell types,” says Dr Sonal Asthana, multi-organ transplant surgeon at Aster Group of Hospitals, who is a part of the team. Five different types of cells, including liver cells called hepatocytes, are used. A medium similar to blood nourishes them.
The liver tissues will be commercially available next year. Academic, pharma and FMCG research and development entities can use these tissues for medical research. “Currently, there are pilot trials going on with selected prospective commercial customers,’’ says Dr Tuhin Bhowmick, director and cofounder.
What makes it all the more important is that these tissues have been developed indigenously. “All the technologies involved in the research and development of 3D liver tissues, such as hydrogels and 3D bio-printer, were developed in-house,’’ says Chandru.
Kiran Mazumdar-Shaw, chairman and managing director of Biocon Ltd, is all praise for the young team of researchers. “Good to see such cutting-edge innovation being pursued by our scientists in new age startups in life sciences,’’ she says. “Bengaluru is consolidating its leadership in tech startups and innovation. Our scientists and engineers have done us proud in driving pathbreaking science overseas and it is indeed great to see this being mirrored in our own country.”
Chandru and his team of researchers are planning to work on developing bio-artificial livers, followed by implantable artificial livers. Their areas of interest include manufacturing personalised tissue patches and organs for transplant.
Implantable artificial livers could revolutionise the liver transplantation scenario in India, says Dr A.S. Soin, chairman and chief surgeon, Medanta Institute of Liver Transplantation and Regenerative Medicine at Medanta-The Medicity, Gurgaon. “Once the techniques are refined and more stable and larger volume artificial livers are made and applied to large animals, the technology has the potential to generate a supply of artificial livers for humans, which could eliminate the shortage of donor livers for transplant,’’ he says.
That is a ray of hope for liver patients. There is an acute shortage of donor livers in India. Of 25,000 patients suffering from liver failure, only 1,500 undergo transplant. Half the patients with end-stage liver disease die while waiting for the donor.
After several rounds of national level screening, the researchers of Pandorum received the Biotechnology Ignition Grant offered by the Biotechnology Industry Research Assistance Council. Later, they got follow-on funding under the Small Business Innovation Research Initiative scheme of DBT.
Says Dr Renu Swarup, managing director, BIRAC and adviser, DBT, “We will continue to support them throughout their journey. Finances are important but I think it is the mentoring, hand holding and networking support from BIRAC, which has been a crucial enabler.”
Many research groups in other countries have developed similar models. Then what is new in this project? “The extracellular matrix, the 3D architecture and the way one cell communicates with another, is unique to our model,” says Dr Sivarajan Chettiar, a researcher at Pandorum Technologies. “That gives you a better quality in drug testing.”
While Soin has high hopes on the project, he is cautious. “Longevity of these cells is an issue that is yet to be settled,” he says. “The situation in the lab cannot be directly extrapolated to the human body, since complex interactions between various protein molecules circulating in the blood and those present in other tissues/organs that govern liver function in a living human cannot be duplicated under artificial conditions where the liver exists in isolation.’