Development of a manufacturing platform to generate 3D liver organoids with semipermeable coating for allogeneic transplantation
Dr. Hassan Rashidi of University College London discusses his research and what it means for the future of treating childhood liver disease. Co-investigated by Professor Nicholas Green and Professor Brian Davidson.
What is the study looking at?
This study is looking at development of cell therapies, providing a large number of active cells without supporting tissues. These are an attractive alternative to whole organ transplant as they avoid the need for an organ donor and surgery. In addition, treatment can be planned and repeated over a period of months or years. However, cell therapies have yet to impact on clinical care due to the difficulty in producing, delivering and maintaining large cell numbers.
Human pluripotent stem cells (hPSCs) are cells with an unlimited ability for self-renewal and develop into hepatocytes (mature liver cells). Several methods to generate hepatocytes from hPSCs have been described but there are concerns regarding cancer risks.
What the study hopes to achieve
The current project will develop methods for manufacturing stable, healthy spheres of mature liver cells (3D Hepatospheres or 3D Heps) from hPSCs as an off-the-shelf product for transplantation into children with liver disease. The intention is to produce a group of functioning hepatocytes which could be implanted (e.g. under the skin) and removed or renewed as required. This strategy may allow the cells to be transplanted without the need for immunosuppression with its associated side effects and costs.
Why is this research important?
The liver is essential to life as it produces proteins and removes harmful toxins from the blood. If the liver fails, transplantation is the only hope for survival. However liver transplant is far from an ideal treatment due to shortage of donor organs, the risk of the surgery and the issue of rejection.
Although development of 3D organoids has been achieved, the success rate of achieving liver-like cells vary. Also, liver organoids are not yet suitable for humans due to lack of scale and reliance on the use of animal products and undefined components.
What about the future?
Data from this study will be used to apply for funding to further develop the product as a cell-therapy approach to treat and improve outcomes for a range of liver-associated metabolic disorders and acute liver failure in children.