Sheep chimera makes human blood cells.

What has four hooves, fluffy wool and millions of human bone marrow cells? A part-human lamb that could pave the way for curing genetic blood diseases -- such as sickle-cell anemia -- in the womb.

The sheep/human chimera, so named because it contains cells from both species, is the creation of blood researchers at Indiana University School of Medicine in Indianapolis and the Veterans Administration Medical Center in Reno, Nev. The researchers, led by Edward F. Srour of Indiana University, embarked on the project while developing strategies for transplanting bone marrow from unmatched donors.

Physicians use bone marrow transplants to treat a variety of blood diseases, from leukemia to potentially fatal genetic disorders such as beta thalassemia. But in many cases, doctors cannot find a bone marrow donor with the same tissue type as the patient in need of the transplant. This generally rules out transplantation, since an unmatched graft would trigger rejection by the recipient's immune system.

To surmount the problem, Srour and his colleagues hit on the idea of transplanting blood "stem cells" -- which give rise to all types of red and white blood cells -- into diseased fetuses before they develop a functioning immune system. To test their idea, the researchers decided to perfrom the transplant between some widely divergent subjects: an adult human donor and a group of fetal sheep.

Srour's group used a centrifuge and a series of antibodies to separate the tiny stem cells from the human donor's marrow. They selected only those cells that bore a membrane protein called CD34 -- a marker for early stem cells -- but lacked another membrane protein called major histocompatibility complex class II, which the donor cells could use to recognize and attack their new host. The researchers injected the isolated cells into the bellies of seven sheep fetuses still being carried by their dams.

In the March 15 BLOOD, they report that three of the seven fetal sheep took up the human stem cells. Srour's group found that the marrow of two of the fetuses, which were killed for study before birth, contained up to 4 percent human cells. The marrow of the third lamb, which was born in late 1990, consisted of more than 6 percent human cells. At age 3 months, this chimeric lamb also contained mature human blood cells, they found.

Srour says his group plans to adapt the strategy to treat human fetuses with genetic blood disorders that can be diagnosed during the first trimester of pregnancy, before the immune system begins working. Candidates for the treatment would include fetuses with sickle-cell anemia, severe combined immunodeficiency or chronic granulomatous disease, in which the body's white blood cells lack the chemical ammunition to kill disease-causing invaders. "If we can establish a small degree of chimerism [in such patients] using normally functioning cells, then 99 percent of the symptoms would be alleviated," he asserts. He adds that the treatment "is not difficult to administer at all," because it does not require surgery.

Malcolm Moore, a hematologist at Memorial Sloan-Kettering Cancer Center in New York City, agrees. "We could use this technique to treat many genetic diseases of the blood....I'm very excited by these data."