Normal and Neoplastic Stem Cells

Abstract

[evdate 2013-11-25] IAS Distinguished Lecture. Title from opening screen.

Co-organized by Division of Life Science.

Abstract: Stem cells are cells that at the single cell level both self-renew and give rise to differentiated progeny. Self renewal is the property that distinguishes stem cells and progenitors, and in the blood-forming system explains why haematopoietic stem cells (HSCs), not progenitors, are the only cells capable of providing rapid and sustained regeneration of the blood-forming system after ablation by cancer chemo- and radiotherapies. Cancer-free prospectively purified HSCs regenerate the haematopoietic system of patients as rapidly as a marrow or mobilized blood transplant, but without the risk of re-seeding the body with cancer cells. Further, purified allogeneic HSCs can establish donor-specific tolerance to subsequent tissue grafts. However, in contrast to widely-publicized reports of HSC plasticity, we have not been able to show transdifferentiation of HSC to muscle, heart, brain or gut, and conclude that rare cell fusions and incomplete purifications are likely explanations for the other published results. The ability to self-renew is also potentially dangerous, as poorly regulated self renewal is, we believe, a central lesion in all cancers. We have recently shown that myeloid leukaemias in mouse and human are often driven by rare leukaemia (cancer) stem cells which are at the progenitor stage of differentiation, but have activated the self-renewing cell division pathway normally used only by HSCs. Similar cancer stem cells have been isolated in other tumours.

Prof Irving Weissman received his MD from Stanford University in 1965. He was a postdoctoral fellow in Dr. H. S. Kaplan’s laboratory, and was appointed a faculty position in the Department of Pathology, Stanford School of Medicine in 1969. He has been an Investigator of the Howard Hughes Medical Institute, the Karel Beekhuis Professor of Cancer Biology and Chair of the Immunology Program. In 2002 he became Director of the Stanford Cancer/Stem Cell Institute, which was split into the Stanford Institute of Stem Cell Biology and Regenerative Medicine, and the Stanford Cancer Center in 2003. He was Director of both. He stepped down as Cancer Center Director in 2008, but remains Director of the Stem Cell Institute. He is currently Virginia & D. K. Ludwig Professor for Clinical Investigation in Cancer Research, Professor of Developmental Biology and, by courtesy, of Biology.

Prof Weissman is an expert in the fields of hematopoiesis, leukemia, and hematopoietic stem cells (HSC), and most recently, the clonal events leading from HSC to leukemia stem cells. His research also encompasses the phylogeny and developmental biology of the cells that make up the blood-forming and immune systems. He has a laboratory at Hopkins Marine Station of Stanford University, where he studies the histocompatibility systems in colonial protochordate. In recent years his work has included studying the potential of CD47 as a cancer therapeutic and identifying cancer stem cells from a variety of blood and solid cancers.

Prof Weissman received numerous awards including the Robert Koch Prize and the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science. He is a Member of the US National Academy of Sciences and the Institute of Medicine, and a Fellow of the American Academy of Arts and Sciences.

Duration: 84 min.