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Endothelial progenitor cells: trick or treat?
  1. Anthony Mathur
  1. Correspondence to Dr Anthony Mathur, William Harvey Research Institute, Queen Mary University of London/Barts and the London NHS Trust, London, UK; a.mathur{at}gmul.ac.uk

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An understanding of endothelial progenitor cell (EPC) biology offers the tantalising reward of addressing some of the fundamental issues in biology relating to vascular repair as well as a potential solution to the holy grail of coronary intervention—the prevention of restenosis.

However, the paper by Mills et al in this month’s issue of Heart1 (see page 2003) raises further questions in this already complex area of research that is struggling to define a method for characterising EPCs and even the form in which they may exist.2 The work reported here uses two methods to characterise EPCs (one based on surface marker expression and the other on functional capacity) following angioplasty and, interestingly, shows that while the level of circulating “EPCs” with a functional phenotype increases, no increase is seen in the putative progenitor cells (CD34+KDR+) as characterised by surface marker expression. The suggestion is made that these circulating functional EPCs therefore originate from another cell type such as monocytes that are by definition a more “mature” cell type and at variance with early reports in the literature that suggested that circulating primitive cells expressing the CD34+ antigen defined the progenitor population.3

An understanding of the role that EPCs have in the response to vascular injury is not only important for an understanding of the biology involved but is key to developing new strategies applicable to vessel repair and even cardiac regeneration. An understanding of the origin and type of cell that may contribute to vascular repair could be used to develop new ways of optimising this innate homeostatic mechanism to improve the results of coronary angioplasty and stent insertion. It may be that if one believes that circulating EPCs are important in the process of stent endothelialisation, and that by optimising this process an improvement in outcome from stent insertion will be achieved (less in-stent restenosis and decreased stent thrombosis), it is crucial that we can define this particular cell type. As demonstrated in the paper by Mills et al discrepancies occur in the type of assay chosen to measure EPCs.1 While pragmatically one would think that a functional assay is more likely to detect the relevant cell over the expression of cell surface markers the limitations of the assay fall short of clearly indicating that this cell type would ultimately go on to form an intact and fully functional endothelium.

On the other hand the lack of association demonstrated here between what has been considered until recently an acceptable combination of cell surface markers that identify EPCs and this group of functionally active cells draws into question our whole understanding of the process. It has been suggested that cell surface marker expression is a process of active turnover and that a sampling snapshot across a range of cells will identify a different pattern of surface marker expression even though the ultimate fate of the cells remains the same.4 It may well be that the “progenitor cells” defined by expression of CD34 and KDR antigens are indeed the cells that go on to form a functional endothelium; however, during the sampling snapshot the majority of cells were at another stage of phenotypic expression not captured by this assay. Although this explanation would reconcile the discrepancy reported by Mills et al and the earlier work that defined the field in relation to cells that express the CD34+ marker, there is little evidence to support this theory and as much evidence to suggest that functional EPCs, as measured by colony forming assays, originate from another cell type. Clearly an improvement in the understanding of EPC biology is needed. If we accept that the results presented by Mills et al demonstrate a response to angioplasty that is in part mediated by circulating progenitor cell mobilisation from an as yet undefined source then these data add further evidence to the theory of natural repair and offer the potential for this process to be harnessed to develop new therapeutics in humans. However, it is clear that given the mounting controversy in the complex field of endothelial progenitor cell biology that even questions the basic definition of the cell type, we must await the results of ongoing basic research before we can decide whether the endothelial progenitor cell is a biological trick or treat.

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Footnotes

  • Competing interests None declared.

  • Provenance and Peer review Commissioned; not externally peer reviewed.

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