Abstract
BackgroundThe discovery of adult endothelial progenitor cells (EPC) offers potential for vascular regenerative therapies. The expression of CD34 and VEGFR2 by EPC indicates a close relationship with haematopoietic progenitor cells (HPC), and HPC-rich sources have been used to treat cardiac and limb ischaemias with apparent clinical benefit. However, the laboratory characterisation of the vasculogenic capability of potential or actual therapeutic cell autograft sources is uncertain since the description of EPC remains elusive. Various definitions of EPC based on phenotype and more recently on colony formation (CFU-EPC) have been proposed.MethodsWe determined EPC as defined by proposed phenotype definitions (flow cytometry) and by CFU-EPC in HPC-rich sources: bone marrow (BM); cord blood (CB); and G-CSF-mobilised peripheral blood (mPB), and in HPC-poor normal peripheral blood (nPB).ResultsAs expected, the highest numbers of cells expressing the HPC markers CD34 or CD133 were found in mPB and least in nPB. The proportions of CD34+ cells co-expressing CD133 is of the order mPB>CB>BM≈nPB. CD34+ cells co-expressing VEGFR2 were also most frequent in mPB. In contrast, CFU-EPC were virtually absent in mPB and were most readily detected in nPB, the source lowest in HPC.ConclusionHPC sources differ in their content of putative EPC. Normal peripheral blood, poor in HPC and in HPC-related phenotypically defined EPC, is the richest source of CFU-EPC, suggesting no direct relationship between the proposed EPC immunophenotypes and CFU-EPC potential. It is not apparent whether either of these EPC measurements, or any, is an appropriate indicator of the therapeutic vasculogenic potential of autologous HSC sources.
Highlights
The discovery of adult endothelial progenitor cells (EPC) offers potential for vascular regenerative therapies
Assessment of CD34+ cells The expression of CD34 on leukocytes was analysed in 10 bone marrow (BM); 21 cord blood (CB); and 27 mobilised peripheral blood samples from patients for autologous transplant
In all cases throughout this study mPBd showed similar results to mPBp, but results are generally not presented here because numbers were too low for meaningful statistical analysis. mPBd results from a larger series will be presented in a subsequent paper which focuses on the effect of G-CSF administration on circulating EPC
Summary
The discovery of adult endothelial progenitor cells (EPC) offers potential for vascular regenerative therapies. The discovery that mononuclear cells in peripheral blood have the potential to differentiate into endothelial cells and may give rise to de novo vasculogenesis [1,2,3], a process hitherto thought only to occur in the developing embryo, has stimulated growing interest in clinical use of locally injected autologous cells to promote revascularisation of ischaemic tissue These circulating adult endothelial progenitor cells (EPC) appear to share a common precursor with haematopoietic progenitor cells (HPC) which was first recognised in early embryogenesis and termed the haemangioblast [4,5,6]. Haematopoiesis is recognised to depend upon the HPC dose administered for rapid and sustained engraftment, and the haematopoietic potential of the HPC graft is determined by the numbers of CD34-expressing mononuclear cells [7] or by expression of CD133 which may identify an earlier more pluripotent HPC population [8,9,10]
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