Oregon Stem Cell Center result of OHSU research strides

03/23/04

New hub to focus on adult stem cells as organ transplant alternative

PORTLAND, Ore. -- Oregon Health & Science University's fast-growing stem cell research program, which already has made significant strides in the hunt for human disease therapies, now has a place to call home.

The multidisciplinary Oregon Stem Cell Center, the first of its kind in the Northwest, is studying cell and gene therapy as an alternative to organ transplantation for pancreatic and liver disorders, diabetes, cancer and a host of other human diseases. Its focus will be on adult stem cells.

Launched in January, the center is housed among several laboratories on the Marquam Hill Campus, but it will occupy a single floor in the 270,000-square-foot Biomedical Research Building now under construction and to be completed in fall 2005.

Its director, Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics in the OHSU School of Medicine, said the center is a hub for all areas of OHSU's rapidly expanding stem cell biology program. It aims to maximize the potential of various stem cells as therapies for human diseases through a rapid, "bench-to-bedside" approach involving basic research in stem cell biology and preclinical trials of therapies in animal models, followed by human trials.

"This is something we needed but didn't have," said Grompe, who has long studied gene and cell therapy for metabolic genetic diseases, as well as the molecular genetics of a rare, cancer-susceptibility syndrome called Fanconi anemia. "The consensus here at OHSU is that this is an area that is going to be important."

While the center's offerings will widen over time to cover other diseases -- Parkinson's disease and diabetes are considered "hot" areas of stem cell research -- it will concentrate on two areas for now and "build on that."

"My idea is to focus on the liver and the pancreas, and focus on adult stem cells," he said. "Our research already is advanced in liver reconstitution by stem cells and the repair of liver disease. We're clearly identified as one of the leaders in that area."

OHSU researchers like Grompe are wasting no time demonstrating the importance of stem cells. His laboratory is renowned as an international leader in cell therapy for liver and pancreas diseases as an alternative to organ transplantation.

Last year, Grompe published a study showing that bone marrow-derived stem cells from mice can combine with liver cells through cell fusion, which occurs when two or more cells combine to form one cell containing more genetic material than normal. The method reversed liver damage.

Other studies indicate bone marrow stem cells can meld with cells of other tissues, such as brain, spinal cord, lung, intestine and heart muscle.

The center's formation reflects a swell of research at OHSU involving stem cells. Scientists are conducting basic research, including molecular-level studies, in cardiology, endocrinology, genetics, hematology and oncology, neurology, neurological and general surgery, and reproduction.

"Basically all diseases which are currently being treated by organ transplantation are, at least on paper, amenable to cell therapy," Grompe said. "Our hope is that procedures as effective as whole organ transplantation will come out of (the center)."

Of particular interest to School of Medicine scientists are recently discovered clonally self-renewing stem cells. These unique cells have energized stem cell research and are broadening the discipline's appeal to a larger group of scientists because of their ability to generate copies of themselves and further divide into special-purpose offspring.

Clonally self-renewing stem cells come in several forms, such as mesenchymal stem cells, neural stem cells and multipotent progenitor cells, and can be used to create multiple cell types, including nerve cells, liver cells and muscle cells. They can be isolated from mice and primates, including humans, manipulated outside the living organism, and transplanted for reconstituting tissue.

"Their ability to be expanded in culture and then differentiated make them attractive for use in cell therapy," Grompe said.

Dan Dorsa, Ph.D., OHSU vice president for research and professor of physiology and pharmacology in the School of Medicine, said stem cells hold promise for treating many disorders. As a result, OHSU has the potential to make "a very broad impact."

"The use of stem cells for treating diseases will be at the forefront," Dorsa said. "The question we want to answer is: What is it about stem cells that allow them to be viable and take on the roles in the body you hope they will?"

The Oregon facility is one of only a handful of stem cell research centers around the country. Other sites include the University of Minnesota, Stanford University, the University of California, San Francisco, and the University of California, San Diego.

The heart of the center is three core facilities that provide cell development and management services for all campus research. They include:

-- A flow-sorting core to identify and isolate stem cell populations and characterize their progeny using fluorescence. Its primary tool, a fluorescence-activated cell sorter, "fishes out living stem cells and keeps them alive for transplantation and study," Grompe said.

-- A cell isolation core to culture, store and distribute specific stem cells. This will allow many researchers at OHSU rapid and easy access to professionally isolated and maintained, high-quality stem cell sources.

-- A monoclonal antibody production core to develop the large quantities of novel antibodies needed for identifying and purifying specific stem cells. Such a service has not been commercially available. "We'll be able to give cells to the core and get antibodies back for researchers," Grompe said. "And the antibodies don't have to be against stem cells to be effective."

The monoclonal antibody production core will be especially useful to cancer researchers, said Grover Bagby Jr., M.D., professor of molecular and medical genetics, OHSU School of Medicine, and director of the OHSU Cancer Institute.

"Having the capacity to make antibodies is going to be a nice core to have," he said. "I think a good number of cancer researchers will come to use that core. It'll be used right out of the gate."

And that could help scientists better track the progression of cancer, most forms of which are mutant outgrowths of stem cells.

"Understanding the cause of cancer definitely leads squarely into the ballpark of stem cells. We know it's true of leukemia and I suspect it's probably true of all other tissues," Bagby said. "There are a lot of things we can learn about stem cells that can lead to an understanding of how to protect them."

Dorsa and Grompe hope the center bolsters the development of OHSU-born spinoff companies while enhancing the university's partnerships with local and national biotechnology firms. It also could make OHSU more of a target for federal grants.

"There are very likely new industries that will be created by virtue of the new activity of the center," Dorsa said. The antibody core, for example, "will be attractive to commercialization."

The Oregon Stem Cell Center is funded by a three-year, $4.5 million grant from the Oregon Opportunity, the statewide, $500 million biomedical research funding initiative supported by public and private dollars. Three faculty members specializing in stem cell research also will be hired during the next two years.

Dorsa believes the Oregon Stem Cell Center fits in well with the National Institutes of Health's "Roadmap" initiative, which strives to accelerate fundamental discovery and translation of that knowledge into effective prevention strategies and new treatments.

"NIH dollars will be attracted by the stem cell center and the investments it will create," Dorsa said. "We think this one will be well positioned to compete for those dollars."

Source: Eurekalert & others

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