Cloning Milestone: Monkey embryos urged to stem cell stage

Researchers have coaxed cloned rhesus macaque embryos to grow to the blastocyst stage, a developmental benchmark in which cells form a hollow, fluid-filled ball. The accomplishment marks the furthest point that scientists have yet reached in cloning a nonhuman primate.

Scientists have long been interested in human cloning as a therapeutic tool. Unlike reproductive cloning, which is meant to create genetically identical organisms, therapeutic cloning aims to grow embryonic stem cells into tissue that matches a patient’s genetic signature.

Scientists have proposed stem cells as a means to treatments for a wide range of diseases, including Parkinson’s and diabetes.

Last February, a group of South Korean researchers grew cloned human embryos through the blastocyst stage using a set of new techniques (SN: 2/14/04, p. 99: Tailoring Therapies: Cloned human embryo provides stem cells). To see whether a similar technique would work on nonhuman primates, thereby opening up medical-research possibilities, Gerald Schatten and his colleagues at the University of Pittsburgh teamed up with the South Korean group to clone macaques.

Following the South Korean team’s procedure, Schatten’s group started with immature eggs, although most researchers begin with mature eggs. Next, the researchers removed the eggs’ nuclei by using the “squish” method pioneered by the South Koreans. As the name implies, the researchers gently squeezed the nucleus out of each cell instead of drawing it out using a vacuum needle, as most other researchers do.

Schatten’s group then inserted into each egg a donor nucleus isolated from another macaque. The source of those nuclei was either cumulus cells, which surround eggs in the ovaries, or fibroblast cells, which make up connective tissue throughout the body. An electric shock or chemical stimulation encouraged the reconstituted eggs to start dividing into multicell embryos.

A significant percentage of the cloned embryos survived about 4 days, an age at which embryonic stem cells are present. However, the researchers say that the embryos provide little possibility for reproductive cloning. None of 135 cloned macaque embryos transplanted into 25 surrogate mothers produced a successful pregnancy.

Schatten and his team presented the results Dec. 6 at the American Society for Cell Biology meeting in Washington, D.C., and in the Dec. 15 Developmental Biology.

Although Schatten says that he and most other researchers are “unhesitatingly” against human reproductive cloning, he notes that cloning macaques or other primates could be a valuable system for studying therapeutic cloning in people.

“Before I had my niece treated with stem cells for diabetes, I’d want to know in a close animal cousin that this therapy was safe [and] effective,” Schatten says.

However, Robert Lanza of Advanced Cell Technology, a Worcester, Mass.–based company that is also investigating therapeutic cloning, warns that researchers shouldn’t assume that primate models mirror people.

“Obviously, humans are closely related [to nonhuman primates], and there are things we could learn from the system, but I strongly caution against applying data generated in any animal to humans,” Lanza says.