Every year, thousands of people die from liver failure because there are not enough donor organs to transplant. Researchers at Imperial College London have developed a way to grow replacement liver cells from induced pluripotent stem cells (iPSCs) in the lab, and they now want to turn that proof of concept into a scalable, off-the-shelf medicine. The problem is stark: donor organs are scarce, and the quality of donated human liver cells is unpredictable. The team’s approach uses iPSC-derived hepatocytes—cells that detoxify poisons like ammonia—encapsulated in alginate and placed into the abdomen. There, they act as a temporary “mini-liver,” buying time for a patient’s own organ to regenerate. In animal models, these lab-grown cells have already matched the performance of donated human cells at rescuing animals from liver failure. If this project succeeds, it could transform liver failure from a condition that requires a scarce organ transplant into one treatable with an off-the-shelf cell product. The team is now working to make the manufacturing process GMP-compliant, scalable to billions of cells, and safe for human use. The endpoint is a product ready for regulatory discussions and, eventually, a Phase I clinical trial.
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Liver failure causes thousands of deaths every year. Organ transplantation remains the only curative option. Unfortunately, we simply do not have enough donor organs to meet the surging demands of patients. Recent clinical data however supports the possibility of using cells (hepatocytes) instead of organs to treat liver failure. Delivering alginate encapsulated hepatocytes into the abdomen of such patients allows cells to serve as an auxiliary, short-term ‘mini-liver’. In this way, patients can be bridged over the period during which their livers are not working properly until the point at which their liver has sufficiently regenerated to function unaided. Due to the scarcity and unpredictable quality of donor derived primary human hepatocytes (PHH), this source of hepatocytes does not represent a viable long-term solution to address the growing and global unmet medical needs of patients. Hepatocytes derived from stem cells however offer the advantage of being scalable to unlimited quantities while maintaining a highly specific and consistent phenotype. They accordingly have the potential to be an ‘off the shelf, one size fits all’ solution. To that end, our group has been pioneering methodologies to generate hepatocytes from iPSCs (induced pluripotent stem cells). Our most recent data demonstrates hepatocytes generated in this way are on par with PHH in their effectiveness for detoxifying poisons such as ammonia as well as rescuing animals with liver failure. We now wish to translate this proof of concept into a broadly available medicine for patients. To realise this ambition, we need to convert our iPSC-Hepatocyte protocol into a GMP-compliant manufacturing process that allows for the scalable generation of billions of cells suitable for patient use. This project is accordingly designed to enable that development through the following three objectives: (1) development of a GLP-compliant process for alginate-encapsulated iPSC-hepatocyte production that leverages 3D scalable differentiation techniques; (2) demonstration of proof-of-concept efficacy using the scaled iPSC-Hepatocyte product in rodent models of liver failure; and (3) establishment of the product’s safety profile alongside associated potency release assays. The expertise required to deliver this work is uniquely included in the multidisciplinary team we have assembled for this project, comprising specialists in both stem cell/liver biology (Imperial) and bioprocess engineering (CGT Catapult). By demonstrating scalability, efficacy, and safety of our product, the endpoint of this project is designed to best position us for attracting follow on investment. At that point, we will work with regulatory consultants and the MHRA to define additional pharm-tox data required prior to initiating a Phase I clinical study.
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