Adult cells reprogrammed to embryonic state

From the Sept. 2005 JDRF Research Frontline

Researchers at Harvard report they have developed a method for creating therapeutic stem cells by fusing adult cells with embryonic stem cells. This fusion appears to reprogram the adult cell, resetting it to a state that resembles the embryonic stem cell. From that point, it might be coaxed to develop into specialized cells that could be used therapeutically in people.

This technique could be used to create replacement cells that are genetically identical to the donor of the adult cell. In addition, it may permit scientists to derive new human embryonic stem cell lines without the need to use human embryos. The research was led by Kevin Eggan, Ph.D., working with Douglas Melton, Ph.D. JDRF support enabled the research, which is reported in the August 26 issue of the journal Science.

"This research, while interesting and provocative, is still in the earliest stage of development and needs to be confirmed by other groups before we begin to understand its long-range impact," said JDRF Chief Scientific Officer Robert Goldstein, M.D. "It presents another possibility for scientists to explore and demonstrates once again the importance of stem cell research. But it would be a mistake to abandon other areas of diabetes research in general, and embryonic stem cell research in particular, because of this preliminary finding."

Currently, human embryonic stem cells are derived using human embryos either left over from in vitro fertilization procedures or created for research. That process is the major reason why some groups are opposed to embryonic stem cell research.

In the Science study, the researchers combined human skin cells with human embryonic stem cells in the presence of a detergent-like substance that caused the two cell types to fuse. The fused cells were "tetraploid" - meaning they contained the combined chromosomes of both the somatic cells (in this case, skin cells) and the embryonic stem cells, and therefore double the normal amount of DNA as in a human cell.

The fused cells were shown to have the characteristics of embryonic stem cells. They expressed the same genes as embryonic stem cells, even with two kinds of chromosomes (from the adult skin cell, and from the embryonic stem cell). This means that the fused cells must have reprogrammed the skin cell chromosomes so that they expressed the same genes as the embryonic stem cell.

Like stem cells, the fused cells could be grown in culture for long periods. Moreover, these tetraploid cells could be induced to develop into nerve cells, hair follicles, muscle cells, and cells of the stomach lining. This demonstrated the ability of the fused cells to give rise to a variety of different cell types.

Several technological hurdles still remain, with the biggest challenge figuring out a way to eliminate the embryonic stem cell nucleus from the newly created cell so that the fused cell would have a normal number of chromosomes instead of double that amount.

While any therapeutic applications from the new method lie far off, the researchers say that in the short term, it is more likely that the new technique will help to understand how embryonic cells reprogram adult, or "somatic" cells to an embryonic state. But Dr. Eggan told Science he expects that in 10 to 15 years, researchers will be able to use the technique routinely and will no longer need embryos or human eggs to reset adult cells.

"This is another example of how much scientists are learning about human embryonic stem cells in these early years of the research," said Dr. Goldstein.