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Potential Application of Very Small Embryonic Like (VSEL) Stem Cells in Neural Regeneration

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Abstract

We found that murine bone marrow contains a mobile population of Oct-4+CXCR4+SSEA-1+Sca-1+linCD45 very small embryonic like stem cells (VSEL) that are mobilized into peripheral blood (PB) e.g., after pharmacological mobilization with G-CSF or in murine model of stroke. We postulate that, VSEL are a mobile population of epiblast/germ line derived stem cells and play an important role as organ-residing reserve population of pluripotent stem cells that gives rise to stem cells committed to particular organs and tissues – including neural tissue. Moreover, since a similar population of small CXCR4+CD133+CD34+SSEA-4+Oct-4+linCD45 cells resides also in human bone marrow, we asked whether in humans, similarly as in mice, the stroke-related stress may trigger mobilization of these cells into peripheral blood. We noticed in stroke patients an increase in the number of circulating primitive cells expressing the VSEL phenotype. Additionally, we noticed a positive correlation between stroke extensiveness, SDF-1 concentration in serum, and the number of VSEL circulating in the peripheral blood. We conclude that VSEL could have a potential prognostic value in stroke patients, and more important that their role in brain regeneration requires further study.

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Abbreviations

7-AAD:

7-aminoactinomycin D

BM:

bone marrow

BMNC:

bone-marrow nucleated cells

CB:

cord blood

CXCR4:

CXC chemokine receptor 4

ESC:

embryonic stem cells

FACS:

fluorescence activated cell sorting

FSC:

forward scatter

G-CSF:

granulocyte colony stimulating factor

GFAP:

glial fibrillary acidic protein

HGF:

hepatocyte growth factor

HGF/SF:

hepatocyte growth factor/scatter factor

HSC:

hematopoietic stem cells

ISS:

ImageStream

LACI:

lacunar infarcts

LIF:

leukemia inhibitory factor

MAPC:

multipotent adult progenitor cells

MSC:

mesenchymal stem cells

PACI:

partial anterior circulation infarcts

PB:

peripheral blood

PBNC:

peripheral blood nucleated cells

PGC:

primordial germ cells

POCI:

posterior circulation infarcts

PSC:

pluripotent stem cells(s)

RBC:

red blood cells

SC:

stem cell

SDF-1:

stromal derived factor-1

SSC:

side scatter

SSEA-1:

stage specific embryonic antigen-1

TACI:

total anterior ciculation infarcts

TC:

computer tomography

VEGF:

vascular endothelial growth factor

VSEL:

very small embryonic like stem cell(s)

VSEL-DS:

very small embryonic like stem cells-derived spheres

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Correspondence to Mariusz Z. Ratajczak .

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Ratajczak, M.Z., Zuba-Surma, E., Kucia, M., Nowacki, P., Machalinski, B. (2010). Potential Application of Very Small Embryonic Like (VSEL) Stem Cells in Neural Regeneration. In: Ulrich, H. (eds) Perspectives of Stem Cells. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3375-8_14

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