ISOLATION OF A CANDIDATE HUMAN HEMATOPOIETIC STEM-CELL POPULATION

We have identified a rare (0.05-0.1%) subset of human fetal bone marro w cells that contains multipotent hematopoietic precursors. The popula tion of human precursor cells that express Thy-1 and CD34 but no known lineage markers is enriched for clonogenic activity that establishes long-term, multilineage (myelomonocytic and B lymphoid) cultures on mo use marrow stromal lines. Further, the Thy-1+CD34+ subset that takes u p little of the fluorescent mitochondrial dye rhodamine 123 contains v irtually all the cells that establish long-term cultures. In human fet al thymus transplanted into SCID (severe combined immunodeficiency) mi ce, Thy-1+CD34+ fetal bone marrow cells differentiate into T lymphocyt es. In two of nine cases, allogeneic Thy-1+CD34+ cells could engraft i ntact human fetal bone marrow grown in SCID mice, resulting in donor-d erived myeloid and B cells. By extrapolation, the rare human Thy-1+Lin -CD34+ cell population contains pluripotent hematopoietic progenitors; we propose that it is highly enriched for candidate hematopoietic ste m cells.