Angiogenesis, the growth of new blood vessels, is a central process in diverse physiological and pathological situations such as healing of wounds and traumas, cardiovascular disorders, inflammatory conditions such as rheumatoid arthritis, and in cancer growth. The current belief about the source of blood vessel wall endothelial cells (ECs) responsible for vascular growth in adults is that a significant and crucial part of neovascular ECs originate from circulating stem and progenitor cells that are first mobilized from the bone marrow (BM), and subsequently differentiate to mature bona fide ECs and incorporate in the vasculature. This concept has become textbook material, and a common theme in modem vascular and cancer biology.
Importantly, it is widely believed that tumor angiogenesis and cancer growth critically depend on BM derived circulating endothelial precursor cells. Endothelial precursors would thus provide a powerful novel approach to block tumor angiogenesis and cure cancer. Correspondingly, therapeutic transplantation of such stem cells would be a promising approach to restore tissue vascularization after ischemic events. Clinical trials with human patients are currently ongoing based on the circulating endothelial precursor cell dogma.
Now, researchers lead by Dr. Petri Salvén at the University of Helsinki, Finland, and the stem cell research pioneer Dr. Irving Weissman at Stanford University, California, have shown that circulating endothelial precursor cells actually do not exist, and that angiogenesis and cancer growth do not involve or depend on such hypothetical stem cells. (PNAS, in press; online 21.-25.4.). By using endothelial cell specific genomic mouse models and most modern three dimensional cellular imaging technologies, they show that endothelial differentiation is not a typical function of BM derived stem cells, and it has to be an extremely rare event if it occurs at all. However, angiogenic and tumor tissues contain large numbers of BM derived cells such as ordinary white blood cells that often are very close to blood vessel walls, and may therefore have been misinterpreted as blood vessel wall ECs in earlier studies utilizing less advanced technologies.
The results have great practical significance when researchers are trying to focus on novel approaches to cure cancer by targeting the normal cells of the body which supply tumors with blood and nutrients. "Our results will help the researchers to concentrate their efforts on molecular and cellular targets that actually exist" says Dr. Salvén, leader of the Helsinki team.
"It has been a learning experience to try to publish results that demonstrate that a number of fellow research have for years been studying nonexistent cells", Dr. Salven comments. "Issues concerning publication bias and nonaccessibility of negative data are really becoming more and more relevant, just as recently seen also in other fields of biomedicine."
Journal
Proceedings of the National Academy of Sciences