University of Washington scientists have made significant progress toward learning how to repair severely damaged human livers with stem cells.
A team of UW researchers for the first time isolated liver stem cells from human fetuses, grew them in the laboratory for months and infused them in laboratory mice, where they replaced thousands of dead liver cells.
If the experimental work continues successfully in the years to come, the technique could one day repair livers badly damaged by drug overdoses, hepatitis and alcoholism.
"I think it’s a significant first step," said Dr. Nelson Fausto, chairman of the UW Department of Pathology, who led the research.
The technique uses stem cells from aborted fetuses, so money for the research isn’t covered by the ban on federal funding for work using stem cells taken from embryos.
Stem cells are living ancestors of specialized human cells. They both reproduce themselves and give rise to successive generations that become the cells of organs, bone, skin, blood and other parts of the body.
Fausto and his colleagues isolated liver stem cells from aborted fetuses that were donated to research. Research at other institutions shows the cells also may be found in umbilical cords. The UW team pinpointed the difficult-to-identify cells by the proteins they produce and with powerful electronic microscopes.
The team also was able to manipulate the stem cells with special laboratory cultures to become cells of the bile duct, cartilage, fat, bone and blood vessels. Such cells someday also might have the potential to repair damaged tissue.
"We found a bunch of cells with this tremendous capacity to differentiate," Fausto said.
The research was reported in this week’s edition of the Proceedings of the National Academy of Sciences.
Dr. Eric Lagasse, a University of Pittsburgh expert on liver stem cells, said the UW research is important because the scientists were able to both isolate the liver stem cells and grow them into basic liver and bile-duct cells. The next important step would be to prove they actually function as normal liver and bile-duct cells.
"It’s so far the best work on the characterization of stem cells in the human liver," Lagasse said.
Research on stem cells has grown in recent years because of their restorative potential. Extensive investigations have been conducted with mice and other laboratory animals, including work on diabetes, multiple sclerosis, Parkinson’s disease and spinal-cord injuries.
Some stem-cell research on humans also has been conducted, including a recent University of Pittsburgh project involving 15 patients with congestive heart failure whose condition improved after receiving stem cells. And stem cells have been used for years in transplants for patients with leukemia and some blood disorders.
President Bush announced in August 2001 that, because of ethical questions, federal funding for embryonic stem-cell research is limited to existing stem-cell lines.
Some institutions have used private funding for such research, and state funding has been approved by California voters for the work. The research by Fausto and his colleagues was financed by the National Institutes of Health.
The UW team used chemicals to separate the stem cells from 2- to 4-month-old fetal livers, which are more likely to have the so-called progenitor cells than are adult livers. Scientists have not been able to isolate those types of cells from fully developed livers.
The UW researchers then maintained the cells in special lab cultures for up to six months, and at various times infused them into mice with about half of their livers destroyed. The immune systems of the mice were suppressed to prevent rejection of the human cells.
"It was a delight when we saw these cells were capable of [partially] repopulating the damaged liver," Fausto said.
The scientists figured out how to isolate and manipulate the cells while working on another project: developing a lab culture for studying the hepatitis C virus, which infects an estimated 4 million people in the U.S.
From the current research, "we gained tremendous understanding of human embryology, cell origins and how the liver is put together," Fausto said. "That kind of knowledge is absolutely crucial for future research."
