Murine bone marrow (BM) contains a mobile population of CXCR4+SSEA-1+Sca-1+lin−CD45− very small embryonic like (VSEL) stem cells (

Leukemia 2006:20; 857
) that are mobilized into peripheral blood (PB) in SDF-1 dependent manner e.g., after pharmacological mobilization with G-CSF or in murine model of stroke (
Leukemia 2006:20;18
). We proposed that VSEL could be potentially employed in regeneration of damaged brain or spinal cord. Since a similar population of CXCR4+CD133+CD34+SSEA-4+Oct-4+lin−CD45− cells resides also in human BM (
Leukemia 2007:21;297
), we asked whether in humans, similarly as in mice, the stroke-related stress may trigger mobilization of these cells from BM into PB. To address this question, we evaluated a number of VSEL in 60 stroke patients and similar number of age-matched controls. The PB samples were harvested during first 24 h, day +3 and day + 7 after stroke, and compared to normal controls. The circulating VSEL in PB were evaluated by employing

  • RQ-PCR,

  • FACS and

  • direct immunofluorescence analysis.

To perform these studies, first the mRNA was extracted from circulating PB mononuclear cells (MNC) and the expression of pluripotent (e.g., Oct-4, Nanog) and neural specific markers (GFAP, Nestin, β-III-tubulin, Olig1, Olig) was evaluated by RQ-PCR. Next, the circulating PB MNC were analyzed by FACS for the presence of cells that express CXCR4+, CD133+ and CD34+ antigens. Finally, we measured the serum concentration of SDF-1 by ELISA. We found in stroke patients

  • an increase in total number of circulating CXCR4+D133+CD34+ cells,

  • ∼ × 8 increase in expression of mRNA for Oct-4 and Nanog in circulating PB MNC that was subsequently confirmed by immunofluorescence staining for a presence of CXCR4+Oct-4+ cells, and

  • increase in serum concentration of SDF-1.

Additionally, we found a positive correlation between the extensiveness of a stroke and the number of CXCR4+ VSEL circulating in PB. We conclude that the stroke triggers the mobilization of CXCR4+ VSEL. We hypothesize that these cells could have a prognostic value in stroke patients as well as use for regeneration of neural tissues. Currently, we are testing this hypothesis in the murine model of stroke.

Topics:
cerebrovascular accident, embryo, ischemic stroke, stem cells, patents, cxcr4 receptors, cd34 antigens, leukemia, stromal cell-derived factor 1, cd45 antigens

Author notes

Disclosure: No relevant conflicts of interest to declare.

2007, The American Society of Hematology
2007
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