TY - JOUR
T1 - A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood
AU - Sato, Tetsuya
AU - Wakao, Shohei
AU - Kushida, Yoshihiro
AU - Tatsumi, Kazuki
AU - Kitada, Masaaki
AU - Abe, Takatsugu
AU - Niizuma, Kuniyasu
AU - Tominaga, Teiji
AU - Kushimoto, Shigeki
AU - Dezawa, Mari
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science and Joint Research Funds of Life Science Institute, Inc. Mari Dezawa, Shohei Wakao, and Yoshihiro Kushida of the Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, are parties to a co-development agreement with Life Science Institute, Inc.
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by collaborative research development with Life Science Institute, Inc., and by Japan society for the promotion of science (JSPS) KAKENHI (Grant Number 16K11393).
Publisher Copyright:
© The Author(s) 2020.
PY - 2020
Y1 - 2020
N2 - Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities in vitro were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.
AB - Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities in vitro were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.
KW - CD45
KW - SSEA-3
KW - muse cells
KW - peripheral blood
KW - pluripotency
KW - sphingosine-1-phosphate
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U2 - 10.1177/0963689720923574
DO - 10.1177/0963689720923574
M3 - Article
C2 - 32525407
AN - SCOPUS:85086356533
SN - 0963-6897
VL - 29
JO - Cell Transplantation
JF - Cell Transplantation
ER -