Identification of a novel class of human adherent CD34− stem cells that give rise to SCID-repopulating cells

Author:

Kuçi Selim1,Wessels Johannes T.1,Bühring Hans-Jörg1,Schilbach Karin1,Schumm Michael1,Seitz Gabriele1,Löffler Jürgen1,Bader Peter1,Schlegel Paul G.1,Niethammer Dietrich1,Handgretinger Rupert1

Affiliation:

1. From the Department of Hematology/Oncology, University Children's Hospital, Tübingen, Germany; Division of Hematology and Oncology, University Medical Clinic, Tübingen, Germany; University Children's Hospital, Würzburg, Germany; and the Division of Stem Cell Transplantation, St Jude Children's Research Hospital, Memphis, TN.

Abstract

Abstract 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-α) 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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