Functional activity of murine CD34+ and CD34- hematopoietic stem cell populations

The transmembrane glycoprotein CD34 is expressed on human hematopoietic stem cells and committed progenitors in the bone marrow, and CD34-positive selection currently is used to isolate bone marrow repopulating cells in clinical transplantation protocols, Recently, CD34(-) hematopoietic stem cells were described in both humans and mice, and it was suggested that CD34(+) murine bone marrow cells may lack long-term reconstituting ability. In this study, the long-term repopulating ability of CD34(+)Lin(-) vs CD34(-)Lin(-) cells was compared directly using syngeneic murine bone marrow transplantation. Highly purified populations of CD34(+)Lin(-) and CD34(-)Lin(-) cells each are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stent cells; how ever, the number of hematopoietic stem cells in the CD34(+)Lin(-) fraction is approximately 100-fold greater than the number in the CD34(-)Lin(-) fraction. In competitive repopulation experiments, CD34(+) stem cells are better able to engraft the bone marrow than are CD34(-) cells. CD34(+)Lin(-) cells provide both short- and long-term engraftment, but the CD34(-)Lin(-) cells are capable of only long-term engraftment. Ex vivo, the CD34(+)Lin(-) stem cells expand over 3 days in culture and maintain the ability to durably engraft animals in a serial transplant model, In contrast, when CD34(-)Lin(-) cells are cultured using the same conditions ex vivo, the cell number decreases, and the cells do not retain the ability to repopulate the hone marrow, Thus, the CD34(+)Lin(-) and CD34(-)Lin(-) cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution. (C) 1999 International Society for Experimental Hematology, Published by Elsevier Science Inc.