L. Gallacher et al., Isolation and characterization of human CD34(-)Lin(-) and CD34(+)Lin(-) hematopoietic stem cells using cell surface markers AC133 and CD7, BLOOD, 95(9), 2000, pp. 2813-2820
Recent evidence indicates that human hematopoietic stem cell properties can
be found among cells lacking CD34 and lineage commitment markers (CD34(-)L
in(-)). A major barrier in the further characterization of human CD34(-) st
em cells is the inability to detect this population using in vitro assays b
ecause these cells only demonstrate hematopoietic activity in vivo, Using c
ell surface markers AC133 and CD7, subfractions were isolated within CD34(-
)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) cells derived from human cord blood
. Although the majority of CD34(-)CD38(-)Lin(-) cells lack AC133 and expres
s CD7, an extremely rare population of AC133(+)CD7(-) cells was identified
at a frequency of 0.2%. Surprisingly, these AC133(+)CD7(-) cells were highl
y enriched for progenitor activity at a frequency equivalent to purified fr
actions of CD34(+) stem cells, and they were the only subset among the CD34
(-)CD38(-)Lin(-) population capable of giving rise to CD34(+) cells in defi
ned liquid cultures. Human cells were detected in the bone marrow of non-ob
ese/ severe combined immunodeficiency (NOD/SCID) mice 8 weeks after transpl
antation of ex vivo-cultured AC133(+)CD7(-) cells isolated from the CD34(-)
CD38(-)Lin(-)population, whereas 400-fold greater numbers of the AC133(-)CD
7(-) subset had no engraftment ability. These studies provide novel insight
s into the hierarchical relationship of the human stem cell compartment by
identifying a rare population of primitive human CD34(-) cells that are det
ectable after transplantation in vivo, enriched for in vitro clonogenic cap
acity, and capable of differentiation into CD34(+) cells, (Blood, 2000;95:2
813-2820) (C) 2000 by The American Society of Hematology.