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Kevin Eggan: A Better Route to Embryonic Stem Cells

Why do some individuals contract a disease – cancer, diabetes, Parkinson’s – and others not? Or, to put it in more scientific language: What occurs in a human being that sometimes transforms healthy cells into diseased ones?

Asking these big questions means delving into the two most promising, complex, and often debated fields in biomedicine: cloning and stem-cell therapy. Yet neither complexity nor controversy has slowed down Kevin Eggan, an assistant professor of molecular and cellular biology at Harvard University and a researcher at the Harvard Stem Cell Institute.

Eggan, who was recognized Wednesday as Technology Review’s Innovator of the Year, has dedicated himself to using cloning and stem cells to learn why major diseases occur and how to alleviate them. In a paper published in Science magazine last month, he and his colleagues announced preliminary results that might even lead to a quelling of ethical concerns about the use of embryonic stem cells.

Today, a common technique for obtaining embryonic stem cells is to take a nucleus from an adult cell (such as a skin cell) and inject it into a unfertilized egg whose nucleus has been removed. The egg then “reprograms” the adult cell’s nucleus to develop into an embryonic state – without the need for fertilization. The cells divide, forming a blastocyst, from which embryonic stem cells can be harvested.

But this method has several drawbacks: it’s technically difficult, it involves creating and destroying embryos, and it requires donated human eggs. In their latest work, Eggan and his coworkers took a different approach: they fused an entire skin cell to an embryonic stem cell, creating a “hybrid” cell. In doing so, they discovered that the fusion process caused genes from the skin cell to be reprogrammed into an embryonic state.

And, even more promising, the fused hybrid cells had many of the same properties as embryonic stem cells, including the ability to form different kinds of cells – the all-important trait of embryonic stem cells.

While the new technique still requires the use of an embryonic stem cell, it opens up a whole new possibility: that adult cells might be transformed into embryonic stem cells without the need for cloned human embryos. What’s more, human eggs are not needed. The next step: to find out how the embryonic cell reprograms the genes of an adult cell.

That’s where Eggan’s expertise comes in. As a PhD candidate at the Whitehead Institute for Biomedical Research, he was able to do what many scientists considered impossible: clone mice from neurons, the most specialized cells in a body. In the process, he began to focus on a key research problem: how genetic material gets reprogrammed so that a nucleus is reset to the beginning of development.

It’s a similar challenge to the one now facing the Harvard stem-cell team: finding out how the embryonic cell is able to reprogram the adult stem cell. The team’s best-guess is that it will take another decade to achieve that goal. And from there, they can begin to determine how the stem cells differentiate into diseased cells and tissues.

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Tagged: Biomedicine

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