CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors.
The AC133 antigen is a novel antigen selectively expressed on a subset of CD34+ cells in human fetal liver, bone marrow, and blood as demonstrated by flow cytometric analyses. In this study, we have further assessed the expression of AC133 on CD34+ cells in hemopoietic samples and found that there was a highly significant difference between normal bone marrow and cord blood versus aphereses (p <0.0001) but not between bone marrow and cord blood. Most of the clonogenic cells (67%) were contained in the CD34+AC133+ fraction. Compared with cultures of the CD34+AC133- cells, generation of progenitor cells in long-term culture on bone marrow stroma was consistently 10- to 100-fold higher in cultures initiated with CD34+AC133+ cells and was maintained for the 8-10 weeks of culture. Only the CD34+AC133+ cells were capable of repopulating NOD/SCID mice. Human cells were detectable as early as day 20, with increased levels (67%) apparent 40 days post-transplantation. Five thousand CD34+AC133+ cells engrafted about 20% of the mice, while no engraftment was observed in animals transplanted with up to 1.2 x 10(5) CD34+AC133- cells. The CD34+AC133+ population was also enriched (seven-fold) in dendritic cell precursors, and the dendritic cells generated were functionally active in a mixed lymphocyte reaction assay. AC133+ cells should be useful in the study of cellular and molecular mechanisms regulating primitive hemopoietic cells.
de Wynter
E A
EA
CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Withington, Manchester, United Kingdom.
Buck
D
D
Hart
C
C
Heywood
R
R
Coutinho
L H
LH
Clayton
A
A
Rafferty
J A
JA
Burt
D
D
Guenechea
G
G
Bueren
J A
JA
Gagen
D
D
Fairbairn
L J
LJ
Lord
B I
BI
Testa
N G
NG
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010455:Peptides / Q000502:physiology*; D013997:Time Factors
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse