Boosting Stem Cells to Treat Diabetes

BUFFALO, N.Y. -- For diabetes patients, who can't produce their own insulin, human stem cell-based transplants that produce insulin would be a major breakthrough.

But current laboratory methods of culturing human stem cells result in very limited quantities, far short of the quantities necessary for therapeutic applications.

For that reason, Emmanouhl (Manolis) Tzanakakis, Ph.D., is striving to boost the numbers of stem cells produced in the laboratory, expanding the pool of cells that eventually can be differentiated into insulin-producing cells.

Tzanakakis, assistant professor in the Department of Chemical and Biological Engineering in the University at Buffalo School of Engineering and Applied Sciences, has received a $200,000 James D. Watson Investigator Grant award to support his studies from the New York State Office of Science, Technology and Academic Research (NYSTAR). He is one of six researchers throughout the state to receive the award this year.

His ultimate goal is to conduct research to develop methods that will allow sufficient quantities of differentiated cells that secrete insulin to be produced from the stem cells. Such cells could be used for diabetes therapies, including transplantation into patients, freeing them from the lifelong necessity of daily insulin injections.

"One of the main obstacles to using stem cells as any kind of human treatment is that you need many more cells than now can be produced in laboratory systems," said Tzanakakis. "The key questions are, 'How do you generate large quantities of cells for patients?' and then 'How do you get them to differentiate to a specific cell type?'"

Working with adult and embryonic stem cells derived from both mice and humans, Tzanakakis and other groups use bioreactor systems, vessels containing growth media and stem cells, that have the potential to produce high densities of undifferentiated cells.

He noted that success will require enhanced understanding of the molecular mechanisms that regulate self-renewal, or regeneration, of stem cells.

"With sound engineering and the application of biological principles, I believe we can achieve large-scale expansion of stem cell production," he said.

He also is exploring ways of inducing larger numbers of stem cells to differentiate into those that produce insulin, based on an understanding of how the pancreas develops in the embryo.

"Although we are a long way from generating cells identical to native beta cells, using stem cells, we are trying to coax stem cells into becoming insulin-producing cells," he said. "To achieve this, cells are treated with growth factors, which are important to the development of the embryonic pancreas effectively mimicking that developmental process, to some extent."

Before coming to UB in 2004, Tzanakakis held post-doctoral positions at the Diabetes Center in the Department of Medicine at the University of California, San Francisco, and at the Stem Cell Institute in the Department of Medicine at the University of Minnesota.

He also has received funding for this research from the Juvenile Diabetes Research Foundation.

Tzanakakis lives in Amherst.