A new type of stem cell, discovered by UCSF researchers, may open new possibilities for fixing damaged parts of the body while sidestepping the politically and morally thorny issues surrounding embryonic stem cell research.
What’s more, so-called endogenous pluripotent somatic, or ePS, cells could give rise to a new line of companies hoping to harness the potential therapeutic power of the discovery.
Like embryonic stem cells, ePS cells have the ability to become several sorts of cells, such as those that make up the heart, skin, brain, pancreas and other organs. That flexibility, known as pluripotency, could be a huge help for researchers restricted from using embryonic stem cells because those cells must be harvested from embryos.
Some religious organizations, for example, oppose embryonic stem cell research because they consider embryos to be human life. As a result, conservative, anti-abortion lawmakers have largely seized on those concerns to tie up funding for research or research facilities and equipment that study embryonic stem cells.
But unlike embryonic stem cells or induced pluripotent stem cells — which scientists engineer from adult stem cells to become embryonic-like before coaxing them to become specific types of cells — ePS cells are genetically stable and mortal, said University of California, San Francisco, pathology professor Thea Tlsty. That may reduce the risk of cells going rogue and morphing into cancer tumors.
Also, because ePS cells are found in adult tissue, researchers believe they can be extracted from different parts of the body and trained to carry out their healing work in other parts of the body.
The findings, published in a paper Monday in the journal the Proceedings of the National Academy of Sciences, also are significant because scientists have long held that pluripotent stem cells do not exist in the body after the embryonic stage of human development. In fact, Tlsty, who is senior author of the paper, said colleagues at a recent meeting of stem cell researchers described her lab's findings as “an earthquake.”
Somdutta Roy, a postdoctoral fellow in UCSF’s pathology department, is the lead author of the paper. Co-authors are Philippe Gascard, Nancy Dumont, Dr. Jianxin Zhao, Deng Pan, Sarah Petrie and Dr. Marta Margeta.
EPS cells appear to be a rare subpopulation of pluripotent stem cells, and Tlsty and others said more research is needed.
One thing is sure, though: Stem cell research will never be the same.
“Now we can start using these cells and asking what is their full potential," Tlsty said.
Tlsty is working on a grant application with a UCSF colleague, for example, that would fund research to see if ePS cells can be turned into insulin-producing pancreatic islet cells. EPS cells eventually could be used as well to help diabetes patients or people blinded or limited by macular degeneration, she said.
“Think of all the potential clinical problems that can be addressed — neurological degeneration or diabetes or heart failure,” Tlsty said. “All of these things would benefit from a source of cells, such as those without immune-suppressive problems, that could potentially rescue the damaged cells.”
Tlsty’s lab used the same “recipes” for differentiating cells as those developed by researchers of embryonic stem cells and induced pluripotent stem cells, the development of which won Shinya Yamanaka, of the Gladstone Institutes in San Francisco, UCSF and Kyoto University, a Nobel Prize in October.
“Yes, there are concerns about using those two sources (of pluripotent stem cells), but they provided us with a tremendous amount of information,” Tlsty said. “Our studies have used those basic recipes and modified them just slightly to demonstrate pluripotency.
“If we started at the beginning, it would be 20-30 years,” Tlsty said.
Preliminary data suggest that ePS cells exist in parts of the body beyond adult breast tissue, Tlsty said, and in men as well as women.
“We have no idea if they’re different by gender,” she said.
EPS cells don’t appear to be left behind by embryonic stem cells, like pieces of bread dropped on a path to help someone find the way home, Tlsty said. The ePS cells, she said, have different expressions, surface markers and other characteristics than those found with embryonic stem cells.
The National Cancer Institute and the California Institute for Regenerative Medicine — the state’s $3 billion taxpayer-supported stem cell research funding agency — as well as the Avon Foundation and the Cancer League Inc., a Piedmont nonprofit, paid for the Tlsty lab’s ePS research.
"This really could be very exciting," said Patricia Olson, executive director of scientific activities at the San Francisco-based California Institute for Regenerative Medicine, or CIRM. "If verified, I think it could be a big deal."
CIRM was formed after California voters in 2004 passed Proposition 71 in the wake of federal restrictions on embryonic stem cell research. The agency in 2007 awarded Tlsty’s lab a $639,150 grant — one of the first doled out by CIRM — that ran into 2010.
"It's yet another example of a case where our funding has generated data and results and could potentially have a big payoff," Olson said. "This was an observation made several years ago, but it's an observation that goes against dogma, so she gets full credit for being very careful in her research. It allows others to replicate it, which is an important hallmark of science."
EPS cells could become another tool, along with embryonic and induced pluripotent stem cells, for researchers to use. Even among those stem cells, some lines are easier to differentiate into a specific type of cell than others, Olson said, so EPS cells may provide another alternative.
Researchers in Tlsty’s Parnassus Avenue lab originally set out to understand how human cells respond to stress, or injury, due to environmental damage or other factors. What they found in 2006 were cells, which they eventually named ePS cells, that proliferated when other cells around the injury had stopped.
“When tissue is injured, it needs to be healed and you need cells that proliferate,” Tlsty said.
Researchers isolated the cells and did further experiments, eventually discovering that the cells were pluripotent and could help patch wounds.
Was Tlsty surprised by the discovery? “Educated appreciation,” she said. “We appreciated what we were looking at.”
Still, questions remain: How do ePS cells become pluripotent? Can researchers ensure that they behave properly when directed to another part of the body? For which tissues can ePS cells be engineered quickly, accelerating their use in humans?