"Using mouse models, this research demonstrated that bone marrow-derived stem cells can combine with liver cells through a method known as cell fusion," explained Markus Grompe, M.D., a professor of molecular and medical genetics, and pediatrics in the OHSU School of Medicine. "This differs from earlier theories that adult stem cells can somehow be 'transformed' into other cell types. The finding represents an important clarification on how adult stem cells can be transformed into therapeutically useful cells, capable of treating various diseases.
Cell fusion occurs when two or more cells combine to form one cell. The resulting cells contain more genetic material than normal. In a mouse model, for instance, fused liver cells may contain 80 chromosomes, double the amount found in a normal mouse liver cell.
To study the use of adult stem cells in treating liver disease, scientists at OHSU used a mouse model for a genetic disease called tyrosinemia, which causes severe liver damage. The research team used purified adult stem cells to treat these animals. While the transplanted cells resulted in a reversal of the liver damage, this reversal took place through cell fusion, not cell transformation.
Many recent reports have indicated that bone marrow stem cells can turn into other tissues such as brain, spinal cord, lung, intestine, pancreas or heart muscle. Although the OHSU research to date has demonstrated cell fusion only in liver, it is likely that cell fusion is responsible for many of these other cases of stem cell flexibility. The liver is able to heal using these cells. However, it's possible that abnormal fused cells would not function in other regions of the body.
"While this research may help shift the focus of adult stem cell research, we also believe it's a major step forward in utilizing stem cells to regenerate healthy liver cells in humans with liver disease," Grompe said. "The next step in this line of research would be to investigate whether there is a way to induce cell fusion, or speed up the fusion process, which is naturally quite slow and inefficient."
These results may also have applications in research for the burgeoning area of gene therapy. Scientists believe cell fusion may be a practical method for introducing new genetic material to correct mutated or malfunctioning genes that cause disease.
The National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health, funded this research.
Journal
Nature