Systemix, Inc.

Novartis Ag

The Toronto Hospital Research Institute

Lesley J Murray

Judy C Young

D Robert Sutherland

Cord organizer

Myeloproliferative leukemia receptor (mpl) ligands, such as thrombopoietin, act on a primitive subpopulation of human stem cells having the characteristics of self-renewal and ability to give rise to all hematopoietic cell lineages. Thrombopoietin supports both megakaryocytic differentiation and primitive progenitor cell expansion of CD34and CD34sub-populations (CD34Lin, CD34Thy-1Lin, and CD34LinRh123). Thrombopoietin also stimulated quiescent human stem cells to begin cycling. Thus, mpl ligands are useful for expanding primitive stem cells for restoration of hematopoietic capabilities and for providing modified human stem cells for gene therapy applications.

Methods for use of MPL ligands with primitive human stem cells

Methods for use of mpl ligands with primitive human stem cells

Myeloproliferative leukemia receptor (mpl) ligands, such as thrombopoietin, act on a primitive subpopulation of human stem cells having the characteristics of self-renewal and ability to give rise to all hematopoietic cell lineages. Thrombopoietin supports both megakaryocytic differentiation and primitive progenitor cell expansion of CD34,and CD34,sub-populations (CD34,Lin,, CD34,Thy-1,Lin,, and CD34,Lin,Rh123,). Thrombopoietin also stimulated quiescent human stem cells to begin cycling. Thus, mpl ligands are useful for expanding primitive stem cells for restoration of hematopoietic capabilities and for providing modified human stem cells for gene therapy applications.

Methods for use of Mpl ligands with primitive human stem cells

Myeloproliferative leukemia receptor (mpl) ligands, such as thrombopoietin, act on a primitive subpopulation of human stem cells having the characteristics of self-renewal and ability to give rise to all hematopoietic cell lineages. Thrombopoietin supports both megakaryocytic differentiation and primitive progenitor cell expansion of CD34.sup.+ and CD34.sup.+ sub-populations (CD34.sup.+ Lin.sup.-, CD34.sup.+ Thy-1.sup.+ Lin.sup.-, and CD34.sup.+ Lin.sup.- Rh123.sup.lo). Thrombopoietin also stimulated quiescent human stem cells to begin cycling. Thus, mpl ligands are useful for expanding primitive stem cells for restoration of hematopoietic capabilities and for providing modified human stem cells for gene therapy applications.

Methods for use of Mpl ligands with primitive human hematopoietic stem

The invention relates to methods of obtaining compositions enriched in hematopoietic stem cells by separating out an enriched fraction of cells expressing the marker CDw109. Methods of obtaining compositions enriched in hematopoietic megakaryocyte progenitor cells are also provided. Compositions enriched for stem cells and populations of cells obtained therefrom are also provided by the invention. Methods of use of the cells are also included.

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San Jose, CA, United States of America

Lesley J Murray