SUSTAINED, RETRANSPLANTABLE, MULTILINEAGE ENGRAFTMENT OF HIGHLY PURIFIED ADULT HUMAN BONE-MARROW STEM-CELLS IN-VIVO

Data from many laboratory and clinical investigations indicate that CD 34(+) cells comprise approximately 1% of human bone marrow (BM) mononu clear cells, including the progenitor cells of all the lymphohematopoi etic lineages and lymphohematopoietic stem cells (stem cells). Because stem cells are an important but rare cell type in the CD34(+) cell po pulation, investigators have subdivided the CD34(+) cell population to further enrich stem cells. The CD34(+)/CD38(-) cell subset comprises less than 10% of human CD34(+) adult BM cells (equivalent to <0.1% of marrow mononuclear cells), lacks lineage (lin) antigens, contains cell s with in vitro replating capacity, and is predicted to be highly enri ched for stem cells. The present investigation tested whether the CD34 (+)/CD38(-) subset of adult human marrow generates human hematopoiesis after transfer to preimmune fetal sheep. CD34(+)/CD38(-) cells purifi ed from marrow using immunomagnetic microspheres or fluorescence-activ ated cell sorting generated easily detectable, long-term, multilineage human hematopoiesis in the human-fetal sheep in vivo model, In contra st, transfer of CD34(+)/CD38(-) cells to preimmune fetal sheep generat ed only short-term human hematopoiesis, possibly suggesting that the C D34(+)/CD38(+) cell population contains relatively early multipotent h ematopoietic progenitor cells, but not stem cells. This work extends t he prior in vitro evidence that the earliest cells in fetal and adult human marrow lack CD38 expression. In summary, the CD34(+)/CD38(+) cel l population has a high capacity for long-term multilineage hematopoie tic engraftment, suggesting the presence of stem cells in this minor a dult human marrow cell subset. (C) 1996 by The American Society of Hem atology.