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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