Mobilization of CD34+ hematopoietic cells, colony-forming cells and long-term culture-initiating cells into the peripheral blood of patients with an acute cerebral ischemic insult

Abstract

In vitro and in vivo data indicate that stem cells found in the bone marrow (BM) are capable of differentiating into neural cells. The aim of this study was to investigate whether potentially pluripotent hematopoietic stem and progenitor cells are recruited from the BM into the peripheral blood as a reaction to ischemic damage of neural tissues. The number of CD34+ cells, colony-forming cells (CFC) and long-term culture-initiating cells (LTC-IC) was measured within 24 h and on day 7 after stroke onset by flow cytometry, or in functional assays in the peripheral blood of 10 patients with acute middle cerebral artery infarct. The National Institute of Health stroke scale, Barthel index and modified Rankin scale were used to monitor the clinical outcome. In four patients receiving intravenous thrombolytic therapy (tissue plasminogen activator; TPA), no significant increase of CD34+ cells, CFC or LTC-IC was detected. In six patients without thrombolytic treatment, the mean number of CD34+ cells/mL increased significantly from 1181+/-248 at day 1 to 3001+/-881 at day 7. Accordingly, the numbers of CFC and LTC-IC increased 2.7- and 1.7-fold. Granulocyte colony-stimulating factor and neutrophil elastase were monitored by ELISA and remained unchanged during the study period. Our results showed a recruitment of hematopoietic progenitor cells from the BM into the peripheral blood after acute ischemic stroke when no thrombolytic treatment was given. Increased progenitor cell recruitment might be caused by so far unknown signaling stimuli of the ischemic penumbra for stem cell mobilization.