Stem cell work at University of Rochester points to progress
A stem cell is like a teenager trying to decide what to be when it grows up.
What makes one kid become a doctor while another develops into an engineer or athlete, a teacher or computer programmer? What makes a cell that could become anything turn into bone, cartilage, muscle, blood — even fat?
Answering that question and then using that knowledge to find treatments is the core of stem cell research at the University of Rochester Medical Center.
That knowledge also may help scientists determine how stem cells differ from other cells in the body. Once scientists know, they can attack diseased cells while protecting healthy ones. Scientists also could find ways to boost those cells to treat neurological disorders and arrest cancer, repair heart muscle or renew blood so there’s less reliance on donors.
Much of that work still is in pipettes and Petri dishes. But in two cases, where modifying existing medications to target stem cells could fix fractures or alleviate the effects of “chemo brain,” research is getting closer to reality.
The medical, and economic, implications have led stem cell research and regenerative medicine to be one of four Innovative Science Programs highlighted in URMC’s 2007-2012 strategic plan.
“The whole idea is to predict the future when you’re creating a strategic plan,” said Dr. Bradford C. Berk, chief executive officer of URMC and member of the Empire State Stem Cell Board’s Funding Committee. “I think our success confirms our approach.”
Since 2008, URMC has received or been earmarked for $12.9 million from the state for stem cell research. That the school has repeatedly received such funds speaks to the quality of the program, according to a Department of Health spokeswoman. Berk recuses himself from funding decisions affecting URMC.
More than 230 scientists in 40 labs housed at the medical center are in various stages of research. The university has received more than $78 million in multiyear grants from various sources, including the National Institutes of Health, for stem cell and related research.
“Part of the reason that stem cells is an important area to get into is the fact that they have the ability to influence all aspects of medicine, and we’re not just investing in the heart, brain or lung,” Berk said. “We’ve seen the growth of stem cell research across the board.”
Most of URMC research is being done with tissue-specific stem cells, which are on their way to being a single kind of tissue, such as brain. These cells are not the more controversial embryonic stem cells, which can give rise to all the cell types of the body. When talking about the complex nature of stem cells, researchers speak in analogies and metaphors to translate scientific concepts into everyday images.
A common metaphor is to compare the progression of a stem cell to the act of baking. You start with flour, but you can end up with a brownie, a bagel or a cupcake. That basic ingredient can turn into many things, depending on the recipe. With a stem cell, how does it wind up as bone or brain tissue?
Scientists are trying to figure out the recipe. Sometimes they work backward — deconstructing the cupcake to see what makes it different from a bagel, even though it started with the same flour. Once they determine how that happened, they can replicate the process to make more cupcakes.
The cell can be replicated in a culture dish and then transplanted into the body, but that requires a sterile environment and other rigorous procedures.
Another way is to use hormones or drugs to boost stem cell production in the body.
For the past five years, J. Edward Puzas and his colleague, orthopedic surgeon Dr. Susan Bukata, have been studying how Forteo, a drug approved to treat osteoporosis, could target the stem cells responsible for healing bone, and then speed that process. The idea came from surgeons such as Bukata, who gave Forteo to 145 patients with stubborn fractures. The surgeons were reporting complete healing among 93 percent of patients in about 16 weeks.
“It was kind of like magic,” said Puzas, senior associate dean for basic research at the URMC.
But the evidence was anecdotal and Puzas wanted to put it to the scientific test.
As a starting point, he and Bukata are conducting a randomized, controlled study on people who have pelvic fractures.
“There are any number of old people whose lives change,” Puzas said. “They are no longer mobile, they’re in wheelchairs, they’re in pain. The fracture never heals. It can be life-threatening because of that. The idea is to keep them as mobile and pain-free as possible. If the fracture doesn’t heal, then they are compromised.”
Puzas said that study results should be available by 2011. “My gut tells me this is going to work.”
Research also is progressing into ways to develop better cancer treatments.
“These agents we use in cancer treatments don’t discriminate,” said Mark Noble, director of the University of Rochester Stem Cell and Regenerative Medicine Institute. “If we can understand what’s different about a normal stem cell and a cancer stem cell, maybe we can kill the cancer stem cell specifically.”
Craig Jordan, head of the URMC cancer stem cell program, and his colleagues are looking at ways to kill leukemia stem cells without killing the blood’s normal stem cells.
Noble published his first paper about stem cell research in 1983. For the past six years, he has led work into identifying why some cancer patients undergoing chemotherapy find themselves in a mental fog. Agents used in cancer treatment kill normal progenitor cells — the rapidly dividing cells that come from stem cells and are responsible for tissue-building. In fact, they may be more vulnerable than the cancer cells.
“That gave us opportunity to discover ways of protecting them,” Noble said.
Noble is preparing to investigate whether a drug that is FDA-approved for another application can stop the cognitive impairment that is an unwanted side effect of chemotherapy.
“That’s very much a branch of stem cell science to my mind, discovering ways to prevent chemo brain,” he said. “What we’re trying to do is protect the stem cells of the body.”
