Human CD34- hematopoietic stem cells: basic features and clinical relevance.

CD34 has been widely used as a stem and progenitor cell marker, and clinical CD34+ stem cell transplantation (CD34+ SCT) has been performed for tumor purging and for prevention of graft-versus-host disease. Recently, CD34-negative hematopoietic stem cells (CD34 HSCs) were identified in mice and humans. Xenogeneic chimera engraftment assays with immunodeficient mice or preimmune fetal sheep resulted in identification of human CD34- HSCs in cord blood, bone marrow, and granulocyte colony-stimulating factor-mobilized peripheral blood, although no significant clonogenic activity was detected in vitro. These characteristics of CD34- HSCs make the assessment of clinical samples difficult. The generation of CD34+ HSCs from CD34 cells in vitro may be a surrogate assay for detecting CD34- HSC activity. This approach was used in recipients of CD34+ SCT and revealed the absence of a CD34 precursor population. The identification of a positive marker in CD34- HSCs and the development of a simpler and more efficient in vivo assay for CD34- HSCs may allow the diagnostic evaluation of human CD34- HSCs in various clinical procedures and diseases.