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

The transmembrane glycoprotein CD34 is expressed on human hematopoietic ste m cells and committed progenitors in the bone marrow, and CD34-positive sel ection currently is used to isolate bone marrow repopulating cells in clini cal transplantation protocols, Recently, CD34(-) hematopoietic stem cells w ere described in both humans and mice, and it was suggested that CD34(+) mu rine bone marrow cells may lack long-term reconstituting ability. In this s tudy, the long-term repopulating ability of CD34(+)Lin(-) vs CD34(-)Lin(-) cells was compared directly using syngeneic murine bone marrow transplantat ion. Highly purified populations of CD34(+)Lin(-) and CD34(-)Lin(-) cells e ach are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stent cells; how ever, the number of hematopoietic st em cells in the CD34(+)Lin(-) fraction is approximately 100-fold greater th an the number in the CD34(-)Lin(-) fraction. In competitive repopulation ex periments, CD34(+) stem cells are better able to engraft the bone marrow th an are CD34(-) cells. CD34(+)Lin(-) cells provide both short- and long-term engraftment, but the CD34(-)Lin(-) cells are capable of only long-term eng raftment. Ex vivo, the CD34(+)Lin(-) stem cells expand over 3 days in cultu re and maintain the ability to durably engraft animals in a serial transpla nt 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 CD3 4(-)Lin(-) cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution. (C) 1999 International Soc iety for Experimental Hematology, Published by Elsevier Science Inc.