Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells.
Here we describe the in vitro generation of a novel adherent cell fraction derived from highly enriched, mobilized CD133(+) peripheral blood cells after their culture with Flt3/Flk2 ligand and interleukin-6 for 3 to 5 weeks. These cells lack markers of hematopoietic stem cells, endothelial cells, mesenchymal cells, dendritic cells, and stromal fibroblasts. However, all adherent cells expressed the adhesion molecules VE-cadherin, CD54, and CD44. They were also positive for CD164 and CD172a (signal regulatory protein-alpha) and for a stem cell antigen defined by the recently described antibody W7C5. Adherent cells can either spontaneously or upon stimulation with stem cell factor give rise to a transplantable, nonadherent CD133(+)CD34(-) stem cell subset. These cells do not generate in vitro hematopoietic colonies. However, their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice induced substantially higher long-term multilineage engraftment compared with that of freshly isolated CD34(+) cells, suggesting that these cells are highly enriched in SCID-repopulating cells. In addition to cells of the myeloid lineage, nonadherent CD34(-) cells were able to give rise to human cells with B-, T-, and natural killer-cell phenotype. Hence, these cells possess a distinct in vivo differentiation potential compared with that of CD34(+) stem cells and may therefore provide an alternative to CD34(+) progenitor cells for transplantation.
Kuçi
Selim
S
Department of Hematology/Oncology, University Children's Hospital, Tübingen, Germany. smkuci@med.uni-tuebingen.de
Wessels
Johannes T
JT
Bühring
Hans-Jörg
HJ
Schilbach
Karin
K
Schumm
Michael
M
Seitz
Gabriele
G
Löffler
Jürgen
J
Bader
Peter
P
Schlegel
Paul G
PG
Niethammer
Dietrich
D
Handgretinger
Rupert
R
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis; D001773:Blood Cells / Q000166:cytology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D006023:Glycoproteins / Q000032:analysis; D006085:Graft Survival; D006410:Hematopoiesis; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D016513:Mice, SCID; D010455:Peptides / Q000032:analysis; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse