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Kim Colavito Markesich
University of Connecticut College of Agriculture and Natural Resources Journal, Fall 2007

           

Less than 150 years ago, scientists had not yet discovered that bacteria caused infection. Today scientists are working on stem cell biology and other sophisticated aspects of contemporary biological research. Theodore Rasmussen, assistant professor of animal science, has recently completed a study in which he successfully reprogrammed the genes of ordinary adult cells — somatic cells — to an embryonic state.

Rasmussen’s work with stem cell research is funded through a five-year NIH grant, as well as with support from the Connecticut Stem Cell Program, UConn, and private foundations. He is involved in several collaborative projects that include scientists from complementary departments including Rachel O’Neill, associate professor in the Department of Molecular and Cell Biology; Winfried Krueger, assistant professor in the Department of Genetics and Developmental Biology, at the UConn Health Center; and Dominic Ambrosi, a doctoral student in molecular and cell biology in Rasmussen’s lab.

Using a mouse model, the team reprogrammed differentiated adult cells, in this case skin cells, back to a gene expression state, which is developmentally equivalent to an embryonic stem cell.

The team works with mice because the genetics are completely defined, and interestingly, mouse cells are very similar to human cells. “It’s a great model system to use before translating it to human studies,” Rasmussen says.

By fusing two cell types together, a skin cell and an embryonic stem cell, the team created a tetraploid cell, or a cell containing chromosomes from both cell types. The new cell returned to a state similar to an embryonic stem cell. “It proves the principle that we can reprogram somatic cells to an embryonic state,” Rasmussen says. “It was an interesting and successful first step.”

The next stage is to isolate the biochemical activity in the embryonic cell without keeping any of the DNA. This biochemical activity is needed to manipulate a differentiated cell and return it to an embryonic state. The goal is to create an embryonic cell type without any foreign DNA that might cause rejection in the recipient. Then the reprogrammed cells, with the individual’s own DNA, could be coaxed to develop in vitro into whatever type of cell is necessary, and then be transplanted into the recipient without fear of rejection or the need for immunosuppressive drugs.

This method would eliminate the need to use donor embryonic stem cells, which are not immunologically matched to prospective patients. By using only the bioactivity from existing embryonic stem cells rather than the complete cell, scientists could create billions of custom cells necessary for any future medical procedures to treat an unlimited number of patients. Embryonic stem cells are immortal, which means an infinite supply of cells could be created from one currently existing embryonic stem cell line.

Rasmussen describes the evolution of this research. “The first generation was nuclear transfer and cloning. [Professor of animal science and director of the Center for Regenerative Biology]  Jerry Yang was instrumental in this process. None of this current research would be going on without that.”

He continues, “The second generation is research like we’ve been doing, the fusion approach, where we showed that we could reprogram embryonic stem cells. And in the future, we’ll work on differentiation, and exploring the potential of stem cells and turning them into useful cell types.”

“I think there is a collective push in the entire stem cell community to be able to come up with directly reprogrammed cells that are immunologically matched,” he says.

            In a current study Rasmussen is doing just that, exploring differentiation and how these stem cells, or cells similar to stem cells, can be transformed into other cell types. “We’re trying to explore the potential of stem cells and understand the molecular and genetic mechanisms that govern how these can be turned into functional cell types.”

            This research may one day lead to treatment for hundreds of diseases. For instance, Parkinson’s disease is caused when brain cells fail to secrete the neurotransmitter dopamine. Currently, physicians try to replace that dopamine with pharmaceutical intervention. Through cell-based therapy, physicians would inject new cells into a patient, and these new cells would alleviate symptoms of Parkinson’s disease by restoration of proper dopamine production.

            In the meantime, scientists such as Rasmussen and his team continue to move science forward one step at a time. He says, “It’s fun doing something that could one day contribute to treating humans suffering from diseases for which there is no hope right now.”