Blood Cells Traced to a Common Ancestor

Article excerpt

After years of sifting through thousands of bone marrow samples, California researchers announced this week that they have identified a candidate "pluripotent" human blood cell - the elusive, primordial cell thought to serve as a fount replenishing red and white blood cells throughout a person's life.

The pluripotent blood cell has been the Holy Grail of hematology because it may hold the key to cures for a host of genetic disorders, leukemias and immune-system diseases such as AIDS. But the purported discovery has already generated controversy among hematologists, some of whom question the thoroughness of the experiments that led to the new finding.

Irving L. Weissman, a noted immunologist at Stanford University, reported the discovery at the 15th Bristol-Myers Squibb Symposium on Cancer Research, held in Seattle. Weissman told the conference that he and his colleagues at SyStemix Inc., a biotechnology company he founded in Palo Alto, Calif., had isolated a human pluripotent cell that can generate nearly every type of human blood cell when transplanted into the bone marrow of mice lacking an immune system. He claims that the cell is the most basic known "stem" blood cell, from which arises the family tree of more specialized blood cells.

To track down the pluripotent cell, the researchers used a series of antibodies against cell-surface proteins that identify the "cluster of differentiation" (CD) of each specific blood cell type. Blood cells that perform different jobs - such as antibody-producing B-cells, or invader-gobbling macrophages - wear different CD-protein uniforms, which are assigned a number as they are found by immunologists. Moreover, just as lieutenants's uniforms differ from those of generals, blood cells don new uniforms as they mature and are promoted to new roles.

Because Weissmann and his colleagues reasoned that blood-cell precursors must persist throughout life, they began their quest among a set of bone marrow cells that had already survived for months in their laboratory. They eventually narrowed their search to a subset of slow-growing cells that stained weakly with the dye rhodamine - an indication that the cell's energy-producing mitochondria were merely idling.

When the researchers added these human marrow cells, one by one, to connective-tissue cells taken from mouse marrow and grown in the laboratory, they found one type of cell that could give rise to all major blood-cell varieties. These cells stuck to a mixture of labeled antibodies that detected the CD34 protein and another protein - called Thyl - that is present on T-cells, white blood cells that mature in the thymus. The same cells also lacked a set of CD proteins, collectively known as the lineage determinants (Lin), normally found on mature blood cells. Weissman's group named the precursor cursor cells [Thyl.sup.+.Lin.sup.-CD34.sup+.]

To prove that these cells could give rise both to lymphoid cells (produced in the lymph nodes, thymus or spleen) and to myeloid cells (made in the bone marrow), the researchers injected some of the cells into the bone marrow of immunodeficient mice, and others into human thymus tissue transplanted into a second group of immunodeficient mice (SN: 9/24/88, p. …