The role of stem cells in developing new drugs

The potential therapeutic applications of stem cells – such as regenerating damaged tissues or organs – have generated a great deal of interest over the past decade. While these types of applications are exciting, it is a long journey from lab to clinic. The most immediate impact of stem cells on human health will most likely come from their use in the development of new drugs.

The ability to generate stem cells by reprogramming cells from patients’ skin has revolutionised human stem cell research. These cells, known as human induced pluripotent stem cells (hIPSC), can be differentiated into almost any cell type, allowing the opportunity to have a ready source of human cells for testing new therapies.

DefiniGEN, a new spin-out company from the University of Cambridge, has been formed to supply hIPSC-derived cells to the drug discovery and regenerative medicine sectors. The company is based on the research of Dr Ludovic Vallier, Dr Tamir Rashid and Professor Roger Pedersen of the Anne McLaren Laboratory of Regenerative Medicine.

Dr Vallier led a team, including Dr Rashid, Dr Nick Hannan and Candy Cho, that developed the technology to generate human liver cells (hepatocytes) in a highly reproducible and scalable manner for commercial use. This represents a major breakthrough in the costly and time-consuming process of developing new therapies. The technology has also been used to effectively model a diverse range of inherited liver diseases and has the potential to accelerate the development of new therapies for these conditions.

The liver is the key organ for metabolising drugs and removing toxins from the body. Consequently, it is often affected by toxic compounds. Demonstrating that a new drug candidate is free from liver toxicity is a key test in the development process, and it is a test that most drug candidates fail.

“If a drug’s failure occurs in the clinical phase of development, a great deal of time and money will have been lost,” said Dr Vallier. “Therefore, identifying toxic drugs as early as possible is vital to the safety and efficiency of the drug discovery process.”

Currently, either primary human hepatocytes or immortalised cell lines are used for toxicity testing. Primary hepatocytes have a high degree of batch-to-batch variation, are expensive and difficult to obtain in suitable quantities, while immortalised cell lines are an inferior model for toxicity testing.

The hIPSC-derived cells produced by DefiniGEN, however, show many of the functional characteristics of primary cells, are highly reproducible and can be made in large quantities, making them ideal for toxicity testing.

In addition, the company’s OptiDIFF platform has produced libraries of disease-modelled cells for a range of diseases, including the most common inherited metabolic conditions such as Familial hypercholesterolemia and Alpha 1 anti-trypsin disorder. The cells effectively demonstrate key pathologies of diseases and can be used to improve lead optimisation studies, assisting the development of new therapies for these conditions.

The company will also develop pancreatic beta cell products which, in combination with hepatocyte products, will enable the optimised development of new therapeutics for diabetes.

“This is a technology whose time has come,” said Dr Marcus Yeo, DefiniGEN’s CEO. “Cambridge has more expertise in the area of stem cells than perhaps anywhere else on earth, and now we are starting to see promising commercial opportunities which build on that expertise.”

DefiniGEN is based in Cambridge, and has been funded by a group led by Cambridge Enterprise, the University’s commercialisation arm, along with members of Cambridge Angels and Cambridge Capital Group.