February 23 2006
9:30 LSB 2320
Whitehead Institute for Biomedical Research
Hematopoietic Stem Cells: Novel Surface Markers And New Growth Factors For Their Expansion
Abstract:
The biological study and clinical applications of hematopoietic stem cells (HSCs) have been severely hampered by the difficulty in ex vivo expansion of these cells and the lack of understanding of the extracellular and intracellular signals that govern their fates. I isolated a novel stromal cell population from fetal liver that supports HSC expansion, and identified IGF-2 and several angiopoietin- like proteins as new HSC growth factors. These studies have enabled me to set up a serum-free culture system that achieves 24-30 fold of ex vivo HSC expansion, measured by bone marrow reconstitution analysis.
In parallel, I identified the normal prion protein (PrP) as a surface protein characteristic of freshly isolated BM HSCs, and showed that PrP on HSCs plays an important role in serial, sustained, hematopoietic engraftment. These have open up new lines of research that furthers the study of the molecular mechanisms by which the cell fates of adult stem cells are regulated, and may be useful for the development of new strategies of cell therapy and gene therapy.