Becton Dickinson and Company Limited

Fridtjof Lund-Johansen

Johanna Olweus

Leon W Terstappen

Michael R Loken

Peter Thompson

Shiang Huang

The expression of various cell adhesion molecules and growth factor receptor was examined on human progenitor cells (i.e., CD34 /CD38 ). Certain changes in the expression if one or more of these molecules and receptors correlates with the progression of cell from non-lineage committed to commitment to a specific lineage. Using one or more markers for these molecules and/or receptors in combination with markers for CD34 and CD38 will enable one to identify and isolate each of the different progenitor cell populations.

Method to distinguish hematopoietic progenitor cells

The present invention demonstrates that M-CSF responsiveness and the M-CSFR expression can be used to discriminate monocytic and granulocytic cells within a population of cells which strongly expresses the CD34 antigen (CD34.sup.hi). Briefly, the method comprises isolating phenotypically and functionally defined CD34.sup.+ subsets, and staining with anti-M-CSFR monoclonal antibodies to measure expression on these primitive progenitors and cells committed to the granulocytic and monocytic lineages, based upon expression of M-CSFR. CD34.sup.hi M-CSFR.sup.hi cells are highly clonogenic and approximately 70% of the colonies are CFU-M (monocytic), whereas less than 20% were CFU-G (granulocytic). In contrast, CD34.sup.hi cells that were positive for the granulo-monocytic marker CD64 and negative for the M-CSFR contained high frequencies of 91% pure CFU-Gs. After 60 h in culture, CD34.sup.hi M-CSFR.sup.hi cells developed into distinct populations of M-CSFR.sup.hi and M-CSFR.sup.lo cells. These two populations gave rise almost exclusively to monocytes and granulocytes, respectively. This result demonstrates that M-CSF target specificity among human hematopoietic progenitor cells is determined by lineage-specific regulation of the M-CSFR and demonstrate that M-CSFR is a useful marker to discriminate CFU-Ms from CFU-Gs.

Differentiation of granulocytic and monocytic progenitor cells

One or more population of cells enriched for human hematopoietic stem cells is disclosed. HSC in this population of cells are capable of limited self-renewal and are capable of differentiating into all elements of the hematopoietic system. This population of cells has the phenotype of CD34.sup.+ /CD38.sup.- and more preferably CD34.sup.+ /CD38.sup.- /HLA-DR.sup.+. Cells within this population have been found to express CD13, CD33 and CD71. Hematopoietic stem cells can be used in a number of therapies, including autologous transplantation and in gene therapy.

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Fremont, CA, United States of America

Fridtjof Lund-Johansen