Circulating CD34-Positive Cells Provide an Index of Cerebrovascular Function

Abstract

Background-Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34-and CD133-positive cells present in peripheral blood, in maintenance of the vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction. Methods and Results-The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34-and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34-and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion. Key Words: cerebral infarction Ⅲ cerebral ischemia Ⅲ antigens, CD34 Ⅲ stem cells A lthough it had traditionally been assumed that replacement of damaged endothelium resulted only from outgrowth of preexisting vasculature, recent studies have identified endothelial progenitor cells (EPCs) that appear to contribute to vascular homeostasis and repair. 1 Clinical trials to assess the therapeutic potential of bone marrow-derived mononuclear cells, a rich source of immature cells including EPCs, in hind-limb 2,3 and cardiac ischemia 4 have been initiated and have, thus far, provided promising results. Furthermore, immature cells, including CD34-positive (CD34 ϩ ) cells, have been shown to contribute to maintenance of the vasculature, not only as a pool of EPCs but also as the source of growth/angiogenesis factors. 5 Bone marrow-derived immature cells have also been shown to participate in neovascularization of ischemic brain after experimental stroke. 6 On the basis of these results, we hypothesized that levels of circulating immature cells might be proportional to the resilience of the cerebral circulation to ischemic stress; ie, lower numbers of circulating immature cells might be associated with cerebral ischemia and infarction. Conclusions-These MethodsThe institutional review board of the National Cardiovascular Center approved this study. All subjects provided informed consent. Circulating CD34 ϩ cells in 50 L of peripheral blood were quantified according to the manufacturer's protocol (ProCOUNT, Becton Dickinson Biosciences). To minimize intersample variation for measurements of CD34 ϩ cells, several methods were used: A nucleic ...

Circulating endothelial progenitor cells in Chinese patients with acute stroke

“…Interestingly, we found that the number of EPCs gradually increased through day 7 after acute onset, remained significantly higher until day 14 and returned to baseline by day 28. Although an earlier study that included only a small group of patients had findings similar to the present study, 21 the authors did not investigate the dynamic change in circulating EPCs in patients with hemorrhagic stroke. Therefore, our findings are the first to suggest that EPCs are mobilized to the peripheral blood in response to vascular trauma and may enhance the repair of damaged vessels.…”

Increase in Circulating CD34-Positive Cells in Patients with Angiographic Evidence of Moyamoya-like Vessels

“…The latter was determined using a newly developed method that enables quantification of few CD34 + cells in peripheral blood in a highly reproducible manner. After acute cerebral ischemia, mobilization of CD34 + cells from bone marrow has been shown in stroke patients (Taguchi et al, 2004a). Furthermore, transplantation of CD34 + cells (Taguchi et al, 2004b) and bone marrow cells (Borlongan et al, 2004a, b) has been shown to restore cerebral blood flow in experimental models of stroke.…”

Circulating CD34-Positive Cells Have Prognostic Value for Neurologic Function in Patients with past Cerebral Infarction

“…Previously, we have shown accelerated neovascularization after administration of CD34 + cells in an experimental model of stroke (Taguchi et al, 2004b), and observed a positive correlation between levels of circulating CD34 + cells and neovascularization (Yoshihara et al, 2008) and regional blood flow (Taguchi et al, 2004a) in patients with chronic cerebral ischemia. In addition, we have delineated a contribution of circulating CD34…”

“…The absolute number of CD34 + cells was calculated using the internal control. On the basis of our previous studies, the cumulative intraassay coefficient of variation of the measurement was 7.4% and test-retest intraclass correlation of the level of CD34 + cells is 0.88 (Taguchi et al, 2004a). For statistical analysis, JMP version 5.1J was used.…”