Two studies may form a tiresome feeling over visions of adult stem cells as a less honestly questionable but nearly equally versatile alternative to embryonic stem cells, whose ability to sprout different cell types has spawned debate between those who think such research destroys a life and those who say it has life-saving potential. The new findings challenge the notion adult stem cells taken from one tissue can directly produce cell types of other tissues and organs. It may be that this capability, revealed in recent research, may arise from a process of fusion that combines two cells into one, and not from one cell changing into another type. Scientists said that such hybrids have double the normal DNA and possibly carry unknown health consequences.
Researchers feel that, whether the process, observed in mouse brain cells in laboratory experiments, also occurs in animals, including humans, remains to be seen. "This suggests a need for caution with regard to the therapeutic use of adult tissue stem cells. If they only make other tissues by fusing with existing cells rather than producing new cells, their utility for tissue repair and regenerative medicine will be greatly restricted," said Austin Smith of the University of Edinburgh in England, lead author of one of the papers.
"While there is justifiably a great deal of interest in the broader applicability of adult stem cells, our findings illustrate that we are currently very ignorant of their biology," Smith said. "It should be noted that although spontaneous cell fusion has been well documented and this work has been overlooked in the recent reports on tissue stem cells."
Studies have shown adult stem cells from one tissue, such as blood, can generate numerous other cell types, such as nerve and muscle, in a fashion reminiscent of embryonic stem cells but without the ethical concerns. These findings -- which the Nature papers now question -- have challenged the traditional view that with the possible exception of those from the brain, adult stem cells are limited to the tissues from which they arise. Many opponents of the creation of stem cells through the removal of an inner cell mass from a 5-to-7-day-old embryo, which is killed in the process, have pointed to adult stem cell research as a viable, less morally offensive alternative to stem cells extracted from embryos. Still in a blank state, embryonic stem cells can turn into any of the cell types in the body.
This morphing power has inspired visions of stem cells one day being used to grow new heart, liver or brain tissue for people whose own organs are damaged, allowing the body to repair itself. Realization of such potential is many years down the road, if ever, scientists cautioned. "There are those who have been expecting a 'quick fix' with stem cells, and these folks will indeed get somewhat of a reality check from these findings," Dr. Arthur Lander, professor and chairman of developmental and cell biology at the University of California, Irvine, told UPI.
The findings -- in separate studies by Smith and team and Naohiro Terada of the University of Florida in Gainesville -- point to an occurrence the previous experiments failed to expose. Adult cells from either the bone marrow or the brain grown in the same dish as embryonic stem cells joined to make hybrid cells able to produce muscle, nerve and other cell types. Studies will be required to confirm that such spontaneous cell fusion between donor and host cells can also take place in animals.
"We decided to publish our rather disappointing discovery about the fusion of stem cells in order to provide very important caution to all scientists now working in this promising area of research," Terada told UPI. "We want the scientific community to know that it is not just important to determine the fact that certain types of stem cells have successfully turned into other types of stem cells -- as a consequence of experiments in test tubes and animal models -- but we need to carefully examine the complete identity of the resulting cell types."
"Practically speaking, what these findings do is send those researchers who have claimed great multipotentiality for adult stem cells back to the lab, to test whether the 'transdifferentiation' they have observed is actually due to cell fusion," Lander said. "Now that they have been made aware of what to look for, it should not take too long before such researchers make the necessary observations to resolve this question."
While the studies showed cell fusion in a petri dish is possible, "that's a long way from showing that fused cells happen often, or that they are responsible for the findings of others in which adult stem cells seemed to show multipotency," Lander told UPI. "If indeed that's the only way such adult stem cells become multipotent, then one would indeed have to be concerned that such cells are clearly not 'normal' in the sense of having too many chromosomes. Such abnormality could be totally benign, or it could cause health problems, e.g. susceptibility to cancer; we just don't know."
"This discovery of fusion in a dish is simply another issue in our evolving understanding of stem cell behavior that needs to be considered, examined and evaluated in multiple experimental systems to see whether is it relevant to (animal) biology or a tissue culture phenomenon," Mark Sussman of the Division of Molecular Cardiovascular Biology at The Children's Hospital and Research Foundation in Cincinnati, Ohio, told UPI. "The potential still exists for stem cells -- even hybrid ones -- to have relevant biological activity and provide (medical) benefit."