Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke

Stroke. 2009 Apr;40(4):1237-44. doi: 10.1161/STROKEAHA.108.535062. Epub 2009 Feb 26.

Abstract

Background and purpose: In a murine model of stroke, we identified a population of very small embryonic-like (VSEL) stem cells (SCs) in adult murine bone marrow that could be mobilized into peripheral blood (PB). This raised the question of whether a similar population of cells is mobilized in human stroke patients.

Methods: We evaluated a number of cells that corresponded to VSEL SCs in the PB of 44 stroke patients and 22 age-matched controls. After each patient's stroke, PB samples were harvested during the first 24 hours, on day +3, and on day +7 and then compared with normal controls. The circulating human cells with the phenotype of VSEL SCs were evaluated in PB by real-time quantitative polymerase chain reaction, fluorescence-activated cell sorting analysis, and direct immunofluorescence staining. In parallel, we also measured the serum concentration of stromal derived factor-1 by ELISA.

Results: In stroke patients, we found an increase in the number of circulating cells expressing SC-associated antigens, such as CD133, CD34, and CXCR4. More important, we found an increase in the number of circulating primitive cells expressing the VSEL phenotype (CXCR4(+)lin(-)CD45(-) small cells), mRNA for Octamer-4 and Nanog, and Octamer-4 protein. All changes were accompanied by an increased serum concentration of stromal derived factor-1. Additionally, we found a positive correlation between stroke extensiveness, stromal derived factor-1 concentration in serum, and the number of CXCR4(+) VSEL SCs circulating in the PB.

Conclusions: We conclude that stroke triggers the mobilization of CXCR4(+) VSEL SCs that have potential prognostic value in stroke patients. However, the potential role of these mobilized cells in brain regeneration requires further study.

MeSH terms

  • AC133 Antigen
  • Aged
  • Aged, 80 and over
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Brain Ischemia / pathology*
  • Brain Ischemia / physiopathology*
  • Cell Count
  • Cell Size
  • Chemokine CXCL12 / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Peptides / genetics
  • Peptides / metabolism
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Regeneration / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stroke / pathology*
  • Stroke / physiopathology*

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Receptors, CXCR4