First stem cells purified from marrow.

First stem cells purified from marrow

Scientists knew where to search, but trying to find stem cells in the bone marrow was like looking for a toothpick in a lumberyard. Though they give rise to the entire blood supply and immune system, stem cells make up only a small fraction of bone marrow cells (0.05 percent in the mouse), and scientists have had only indirect evidence that they exist at all. Now, researchers using refined immunological procedures on mouse bone marrow have succeeded in purifying stem cells for the first time, they report in the July 1 SCIENCE. Similar procedures in humans, though more difficult, might prove helpful in isolating human stem cells and could improve the efficiency and safety of bone marrow transplantation, they add.

Before performing a marrow transplant, doctors check to see that the antigens of the donor's bone marrow closely match those of the recipient's. A mismatch could make the host's immune system reject the donor cells. Since stem cells are only precursors and thus have no antigens that the patient's immune system would recognize as foreign, a stem cell transplantation theoretically would avoid the risk of adverse immune reactions. For this reason, the goal of isolating a pure stem cell population has enticed medical researchers for decades.

To obtain mouse stem cells, Irving Weissman and Shelly Heimfeld of Stanford University School of Medicine in Palo Alto, Calif., and Gerald Spangrude, now at the Royal Melbourne Hospital in Victoria, Australia, sorted types of mouse bone marrow cells by the different antigens on their surfaces. They added antibodies that attached to antigens on certain of the cells, such as red blood cells, B cells or T cells, and then eliminated those cells from the population. To the remaining cells, they applied two other antibodies. Thy-1 and Sca-1, that previous research indicated would bind to stem cells. They saved only those cells that bound to both antibodies.

After the antibody treatment, the researchers injected the selected cells into mice whose bone marrow had been destroyed through irradiation. They then tested the mice for their ability to reconstitute the different blood cell types. The only cells capable of reproducing the mouse's complete blood supply were those that did not attach to the first set of antibodies but did bind to Thy-1 and Sca-1. Weissman and his colleagues also discovered that as few as 30 of these select cells could revive the entire blood supply. "We are very confident that these are all stem cells," says Heimfeld.

Weissman's group is now beginning to explore ways to introduce genes into mouse stem cells. If his team succeeds, its mouse system might serve as a model for gene therapy in humans. Doctors theoretically could remove a patient's stem cells, insert genes needed to correct a genetic defect, and inject the altered stem cells back into the patient, say the researchers. "Now that we have a purified population of stem cells," says Heimfeld, "gene therapy is a feasible technique. It looks very promising."