Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke.
OBJECTIVE
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.
Paczkowska
Edyta
E
Department of Physiopathology, Pomeranian Medical University, Szczecin, Poland.
Kucia
Magda
M
Koziarska
Dorota
D
Halasa
Maciej
M
Safranow
Krzysztof
K
Masiuk
Marek
M
Karbicka
Anna
A
Nowik
Marta
M
Nowacki
Przemyslaw
P
Ratajczak
Mariusz Z
MZ
Machalinski
Boguslaw
B
D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002452:Cell Count; D048429:Cell Size; D054377:Chemokine CXCL12 / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019718:Receptors, CXCR4