Massachusetts General Hospital (MGH) researchers have a developed a totally new approach to treating liver failure – manipulating the immune response.
If the results of the animal study can be applied in human patients, the approach may be able to keep patients alive until donor organs become available or to support liver function until the organ can regenerate itself, eliminating the need for a transplant. The findings are being reported in the journal PLOS One.
“We have identified a non-hepatic source of cells that can easily be expanded to the scale required for clinical application,” says Martin Yarmush, MD, PhD, director of the Center for Engineering in Medicine at MGH, the paper's senior author. He also is the Helen Andrus Benedict Professor of Surgery and Bioengineering in the Harvard-MIT Division of Health Science and Technology (HST) and a senior scientific staff member at the Boston Shriners Burns Hospital.
The liver is one of the few major organs that is able to regenerate itself. But when the organ is damaged by diseases like chronic hepatitis, long-term alcohol consumption, or other causes, ongoing inflammation can increase cell death and suppress the natural regenerative process. The only current treatment for end-stage liver failure is transplantation, which is limited by the organ supply and requires long-term immunosuppressive treatment. While external liver assist devices have successfully supported some patients, such machines require a supply of preferably human liver cells, which have been difficult to acquire and expand.
For their investigation, the MGH research team used mesenchymal stem cells (MSCs) – cells from the bone marrow that develop into tissues supporting blood cell development in the marrow cavity. Previous research has shown that MSCs are able to inhibit several immune system activities. A supply of MSCs can be extracted from a patient's own marrow and expanded to levels that could be therapeutically useful. To evaluate the ability of human MSCs to treat organ failure involving inflammatory activity, the investigators tested several ways of using the cells to treat rats in which liver failure had been induced.