The results of two new studies may completely transform the way scientists worldwide approach the field of stem cell research.
Scientists have long believed that stem cells -- derived from blood, bone marrow or embryos -- are capable of repairing damaged tissue by taking on the identity of that organ's cells, a phenomenon known as differentiation.
But the new studies show that in the diseased livers of mice, stem cells didn't differentiate. Instead, they fused with the injured liver cells to perform the necessary repairs.
The finding is controversial, especially among stem cell researchers who have devoted a lot of energy to uncovering a way to induce the cells to change identity.
"I'm a little bit disappointed with this finding," said Holger Willenbring, an author of one of two papers published in the March 30 issue of Nature and a researcher in Markus Grompe's lab at the Oregon Health and Science University in Portland. "Not extremely, but at first you wanted to believe there was a cell in the adult body which can adopt every phenotype and can repair tissue and be the future of regenerative medicine."
While a magic stem cell in bone marrow that can heal myriad diseases may not exist, the researchers were able to correct liver damage in mice.
"We have shown that you can correct a liver disease with bone marrow transplantation," Willenbring said.
Last year, two studies showed that fusion, not differentiation, was happening when stem cells helped heal tissue in a petri dish. When the results were published in Nature, stem cell researchers around the globe set out to prove the same in a live organism.
Grompe's lab and another group led by David Russell at the University of Washington in Seattle, were the first to do so, in mice.
The researchers irradiated the mice to damage their livers, and then performed bone marrow transplants. After five months, the mice's livers were repopulated with newly formed, healthy liver tissue.
After studying the genetics of the new cells, the researchers found they contained DNA material from both the donor and the recipient mice. That proved that the donor cells fused with the recipient cells, rather than differentiating.
"The very cool thing is that the membranes fuse together and share a common cytoplasm (gel-like substance inside a cell)," Willenbring said.
Bone marrow contains "adult" stem cells, as opposed to stem cells taken from embryos (most often left over from in-vitro fertilization). Stem cells in embryos are clean slates that grow into each type of cell in the body. Blood and bone marrow contain a type of stem cell that continually produces fresh cells.
Researchers have been trying to find ways to coax adult and embryonic stem cells to differentiate into liver, brain, spinal cord and other types of cells to repair injuries.
Although this work was done in adult stem cells of mice, the results might also give embryonic stem cell researchers a new direction in their future research, Willenbring said.
Groups that oppose abortion have looked to adult stem cell research as an answer to the problem they see with embryonic stem cell research. When stem cells are taken from an embryo, it is destroyed, which some believe is the same as murder.
As it turns out, stem cells might not even be necessary in this repair process, according to Russell.
"Based on these studies it's not clear you even need a stem cell to do the fusion," he said. "It's a big open question as to which cell does the fusing."
The next step will be to determine whether the same results will occur in other organs besides the liver.
"The other really big area we have to look at is what's the genomic stability of these cells, because they're not normal anymore," Russell said. The cells contain genetic information from various origins, so it's possible they could be unstable and lead to tumor formation.
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