Following embryonic development, most of our tissues and organs are continuously regenerated from tissue/organ specific stem cells. The principal property that distinguishes such stem cells from their daughter cells is self-renewal; when stem cells divide they give rise to stem cells (by self-renewal) and progenitors (by differentiation). In most tissues only the primitive stem cells self-renew. Stem cell isolation and transplantation is the basis for regenerative medicine. Self-renewal is dangerous, and therefore strictly regulated. Poorly regulated self-renewal can lead to the genesis of cancer stem cells, the only self-renewing cells in the cancerous tumor. The Weissman lab has followed the progression from hematopoietic stem cells to myelogenous leukemias. They have found that the developing cancer clones progress at the stage of hematopoietic stem cells, until they become fully malignant. At this point, the ‘leukemia’ stem cell moves to a stage of a downstream oligolineage or multilineage progenitor that has evaded programmed cell death and programmed cell removal, while acquiring or keeping self-renewal. While there are many ways to defeat programmed cell death and senescence, there appears to be one dominant method to avoid programmed cell removal―the expression of the cell surface ‘don’t eat me’ protein CD47, the ligand for macrophage SIRP-alpha. All cancers tested express CD47 to overcome expression of ‘eat me’ signals such as calreticulin and asialogylycoproteins. Antibodies that block the CD47―SIRP-alpha interaction enable phagocytosis and killing of the tumor cells in vitro and in vivo.
Irving L. Weissman received his B.S. from Montana State University and an M.D. from Stanford University. He became Director of the Stanford Cancer/Stem Cell Institute in 2002, which will house the first PhD program devoted to stem cell biology in the nation. He was a founder of three companies, SyStemix, Cellerant, and Stem Cells, Inc., all focused on bringing stem cell therapies into the clinic, and earlier was on the founding SAB’s of Amgen, DNAX, and T Cell Sciences. His main research interests are 1) hematopoietic stem and progenitor cells, 2) central nervous system stem and progenitor cells, 3) lymphocyte differentiation, 4) homing receptors, 5) normal and neoplastic hematolymphoid development, and 6) the phylogeny of stem cells and alloreactivity in protochordates.