New Ways to Make Embryonic Stem Cells

Scientists at Harvard announced today that they can generate cloned stem-cell lines from fertilized eggs in mice. If replicated in humans, the findings could provide a huge boon to the field of human therapeutic cloning. To create genetically tailored stem cells, which experts say is crucial for understanding and treating disease, DNA from an adult cell is inserted into an egg whose DNA has been removed. The egg begins to develop as a normal embryo would, and scientists harvest stem cells after a few days.

However, few women have been willing to donate their eggs for research, and lack of this crucial resource has drastically slowed research efforts. Women are paid thousands of dollars to donate their eggs to fertility clinics, but not for research. (See “Lack of Human Eggs Could Hamper U.S. Cloning Efforts.”) Kevin Eggan, a stem-cell researcher at Harvard, was given approval to start therapeutic-cloning research with human eggs more than a year ago, but was delayed for a full year due to lack of eggs.

In the study, published today in Nature, Eggan and his colleagues removed the chromosomes from newly fertilized mouse eggs and then inserted DNA from an adult skin cell. The eggs began to divide, allowing the researchers to successfully harvest stem cells. The procedure worked even with abnormally fertilized eggs, such as those that had been fertilized by two sperm. Such eggs are routinely discarded during in vitro fertilization because they can’t develop normally, but they might provide a new source of materials for cloning experiments. Eggan now plans to try the procedure with human eggs.

Eggan emphasizes that he and his team started the project for practical reasons–to find an alternative resource for therapeutic-cloning research–rather than for ethical ones. Religious opponents of embryonic stem-cell research and therapeutic cloning, especially those who believe that life begins at conception, are unlikely to be swayed by the new procedure.

Three other papers published today–two in Nature and one in Cell Stem Cell–describe an additional way to generate stem cell-like cells in mice. Three independent groups (in Japan, in Germany, and in the United States) were able to revert fibroblast cells–adult cells found in connective tissue–back to an embryonic stem cell-like state by activating four genes expressed in stem cells.

The cells look and behave like embryonic stem cells, showing similar molecular markers and the ability to differentiate into different cell types. If the procedure is replicated in humans, the findings could provide a way to generate tissue-matched cells for patients requiring cell transplants.

But scientists caution that they don’t yet know if the same four genetic factors will work in human cells. In addition, the method is inefficient: only a small percentage of the cells are effectively reverted back to their embryonic state, suggesting that other, as-yet-unknown signals are likely to be important in the process.