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(Stroke. 2009;40:1237.)
© 2009 American Heart Association, Inc.

Original Contributions

Clinical Evidence That Very Small Embryonic-Like Stem Cells Are Mobilized Into Peripheral Blood in Patients After Stroke

Edyta Paczkowska, MD, PhD; Magda Kucia, PhD; Dorota Koziarska, MD, PhD; Maciej Halasa, MD, PhD; Krzysztof Safranow, MD, PhD; Marek Masiuk, MD, PhD; Anna Karbicka, MD, PhD; Marta Nowik, MD, PhD; Przemyslaw Nowacki, MD, PhD, DSc; Mariusz Z. Ratajczak, MD, PhD, DSc Boguslaw Machaliski, MD, PhD, DSc

From the Department of Physiopathology (E.P., M.H., M.Z.R., B.M.), Pomeranian Medical University, Szczecin, Poland; Stem Cell Institute at James Graham Brown Cancer Center (M.K., M.Z.R.), University of Louisville, Louisville, Ky; and the Clinic of Neurology (D.K., A.K., M.N., P.N.), Department of Biochemistry and Medical Chemistry (K.S.), and Department of Pathology (M.M.), Pomeranian Medical University, Szczecin, Poland.

Correspondence to Mariusz Z. Ratajczak, MD, PhD, DSc, Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 580 S Preston St, Baxter II, Rm 119E, Louisville, KY 40202. E-mail mzrata01{at}louisville.edu or Boguslaw Machalinski, MD, PhD, DSc, Department of Physiopathology, Pomeranian Medical University, 72 Powstancow Wlkp Str, 70-111 Szczecin, Poland. E-mail machalin@sci.pam.szczecin.pl

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.

Key Words: ischemic stroke • very small embryonic-like stem cells • stem cells • mobilization